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CHAPTER
19
Mitochondria,
Chloroplasts, Peroxisomes
T
his chapter considers three organelles formed by posttranslational import of proteins synthesized in the cytoplasm. Mitochondria and chloroplasts both arose from
endosymbiotic bacteria, two singular events that occurred about one billion years
apart. Both mitochondria and chloroplasts retain [besitzen noch] remnants of those
prokaryotic genomes but depend largely on genes that were transferred to the nucleus
of the host eukaryote. Both organelles brought biochemical mechanisms that allow
their eukaryotic hosts to acquire and utilize energy more efficiently. In oxidative
phosphorylation by mitochondria and photosynthesis by chloroplasts, energy from
the breakdown of nutrients or from absorption of photons is used to energize electrons.
As these electrons tunnel through transmembrane proteins, energy is partitioned off
[wird aufgeteilt] to create proton gradients. These proton gradients drive the rotary
[rotierend] ATP synthase (see Fig. 8-5) to make adenosine triphosphate (ATP), which
is used as energy currency to power the cell. Peroxisomes contain no genes and
depend entirely on nuclear genes to encode their proteins. Their evolutionary origins
are obscure. Peroxisomes contain enzymes that catalyze oxidation reactions that are
essential for normal human physiology. Patients who lack peroxisomes have severe
neural defects.
Mitochondria
Evolution and Structure of Mitochondria
Mitochondria (Fig. 19-1) arose about 2 billion years ago when a Bacterium fused with
an archaeal cell or established a symbiotic relationship with a primitive eukaryotic cell
(see Fig. 2-5 and associated text). The details are not preserved in the fossil record,
but the bacterial origins of mitochondria are apparent in their many common features
(Fig. 19-2). The closest extant [heute lebend] relatives of the Bacterium that gave rise
to mitochondria are Rickettsia, aerobic α-proteobacteria with a genome of 1.1 megabase pairs. These intracellular pathogens cause typhus and Rocky Mountain spotted
fever [amerikanisches Zeckenfieber]. However, some evidence argues that the actual
progenitor [Vorfahre] bacterium had the genes required for both aerobic and anaerobic
metabolism.
As primitive eukaryotes diverged from each other, most of the bacterial genes were
lost or moved to the nuclei of the host eukaryotes. The pace of the gene transfer to
the nucleus varied considerably depending on the species, but all known mitochondria
retain some bacterial genes. A very few eukaryotes, such as Entamoeba, that branched
331
332
SECTION VI — Cellular Organelles and Membrane Trafficking
A
B
Figure 19-1 CELLULAR DISTRIBUTION AND STRUCTURE OF MITOCHONDRIA. A, Fluorescence light micrograph of a Cos-7 tissue culture cell with
mitochondria labeled with green fluorescent antibody to the β-subunit of the F1-ATPase and microtubules labeled red with an antibody.
B, Electron micrograph of a thin section of a mitochondrion. (A, Courtesy of Michael Yaffee, University of California, San Diego. B, Courtesy
of Don Fawcett, Harvard Medical School, Boston, Massachusetts.)
well after their ancestors [Vorfahren] acquired mitochondria lost the organelle, leaving behind a few mitochondrial genes in the nucleus.
Chromosomes of contemporary [heutig] mitochondria vary in size from 366,924 base pairs (bp) in the
plant Arabidopsis to only 5966 bp in Plasmodium.
These small, usually circular genomes encode RNAs and
proteins that are essential for mitochondrial function,
including some subunits of proteins responsible for
adenosine triphosphate (ATP) synthesis. The highly
pared-down [verkleinert] human mitochondrial genome
with 16,569 bp encodes only 13 mitochondrial membrane proteins, two ribosomal RNAs, and just enough
tRNAs (22) to translate these genes. The number of
proteins encoded by other mitochondrial genomes
ranges from just 3 in Plasmodium to 97 in a protozoan.
Nuclear genes encode the other 600 to 1000 mitochondria proteins, including those required to synthesize
proteins in the matrix. All mitochondrial proteins that
are encoded by nuclear genes are synthesized in the
cytoplasm and subsequently imported into mitochondria (see Figs. 18-2 and 18-3).
Mitochondria consist of two membrane-bounded
compartments, one inside the other (Fig. 19-2). The
outer membrane surrounds the intermembranous
space. The inner membrane surrounds the matrix.
Each membrane and compartment has a distinct protein
composition and functions. Porins in the outer membrane provide channels for passage of molecules of less
than 5000 D, including most metabolites required for
ATP synthesis. The highly impermeable inner membrane is specialized for converting energy provided by
breakdown of nutrients in the matrix into ATP. Four
complexes (I to IV) of integral membrane proteins use
the transport of energetic [energiereich] electrons to
create a gradient of protons across the inner membrane. The F1F0 ATP synthase (see Fig. 8-5) utilizes the
proton gradient to synthesize ATP. The area of inner
membrane available for these reactions is increased by
folds called cristae that vary in number and shape
depending on the species, tissue, and metabolic state.
Cristae may be tubular or flattened sacs. Contacts
between the inner and outer membranes are sites of
protein import (see Fig. 18-4). Proteins in the inter-
A. Mitochondria
Outer membrane
Inner membrane
DNA
Book icon
Cristae
Matrix
B INTERMEMBRANOUS SPACE
C
I
I
II
III
IV
PERIPLASM
II
MATRIX
III
IV
CYTOPLASM
D. Bacterium
DNA
CYTOPLASM
Periplasmic space
Inner membrane
Outer membrane
Figure 19-2 The compartments of a mitochondrion (A–B) compared with a Bacterium (C–D). Respiratory chain complexes I to IV
are labeled with roman numerals.
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
membranous space participate in ATP synthesis but,
when released into the cytoplasm, trigger [auslösen]
programmed cell death (see Fig. 46-15).
Biogenesis of Mitochondria
Mitochondria grow by importing most of their proteins
from the cytoplasm and by internal synthesis of some
proteins and replication of the genome (Fig. 19-3). Targeting and sorting signals built into the mitochondrial
proteins that are synthesized in the cytoplasm direct
them to their destinations (see Fig. 18-4).
Similar to cells, mitochondria divide, but unlike most
cells, they also fuse with other mitochondria. These
fusion and division reactions were first observed nearly
one hundred years ago. Now it is appreciated that a
balance between ongoing fusion and division determines the number of mitochondria within a cell. Both
fusion and division depend on proteins with guanosine
triphosphatase (GTPase) domains related to dynamin
(see Fig. 22-11). In fact, eukaryotes might have acquired
their dynamin genes from the bacterium that became
mitochondria.
One dynamin-related GTPase is required for division
of mitochondria. This GTPase self-assembles into spirals
that appear to pinch [abschnüren] mitochondria in two.
During apoptosis (see Chapter 46), this GTPase also
participates in the fragmentation of mitochondria.
Fusion involves two GTPases, one anchored in the
outer membrane and the other in the inner membrane,
both linked by an adapter protein in the intermembrane
space. Fusion of the outer membranes requires a proton
gradient across the inner membrane, while fusion of the
inner membranes depends on the electrical potential
across the inner membrane. Loss of function mutations
in fusion proteins lead to cells with numerous small
mitochondria, some lacking a mtDNA molecule. Human
Nuclear genes on nuclear DNA
Over 600 mitochondrial
proteins synthesized
in cytoplasm
Import into
mitochondria
Mitochondrial genes
on mitochondrial DNA
• 13 mitochondrial
membrane proteins
• 22 tRNAs
• 2 rRNAs
Figure 19-3 BIOGENESIS OF MITOCHONDRIA. The drawing shows the
relative contributions of nuclear and mitochondrial genes to the
protein composition.
mutations in the genes for fusion proteins result in
defects in the myelin sheath [Myelinscheide] that insulates axons (one form of Charcot-Marie-Tooth disease)
and the atrophy [Schrumpfung] of the optic nerve.
Mitochondrial fusion proteins are also required for
apoptosis.
Synthesis of ATP by
Oxidative Phosphorylation
Mitochondria use energy extracted from the chemical
bonds of nutrients to generate a proton gradient across
the inner membrane. This proton gradient drives the
F1F0 ATP synthase to synthesize ATP from ADP and
inorganic phosphate. Enzymes in the inner membrane
and matrix cooperate with pumps, carriers, and electron transport proteins in the inner membrane to move
electrons, protons, and other energetic intermediates
across the impermeable inner membrane. This is a
classic chemiosmotic process (see Fig. 11-1).
Mitochondria receive energy-yielding [Energie freisetzend] chemical intermediates from two ancient metabolic pathways, glycolysis and fatty acid oxidation
(Fig. 19-4), that evolved in the common ancestor of
living things. Both pathways feed into the equally
ancient citric acid cycle of energy-yielding reactions in
the mitochondrial matrix:
• The glycolytic pathway in cytoplasm converts
the six-carbon sugar glucose into pyruvate, a
three-carbon substrate for pyruvate dehydrogenase, a large, soluble, enzyme complex in the
mitochondrial matrix. The products of pyruvate
dehydrogenase (carbon dioxide, the reduced form
of nicotinamide adenine dinucleotide [NADH],
and acetyl coenzyme A [-CoA]) are released into
the matrix. NADH is a high-energy electron carrier.
Acetyl-CoA is a two-carbon metabolic intermediate that supplies the citric acid cycle with energyrich bonds.
• Breakdown of lipids yields fatty acids linked to
acetyl-CoA by a thioester bond. These intermediates are transported across the inner membrane of
mitochondria, using carnitine in a shuttle system.
In the matrix, acyl-carnitine is reconverted to acylCoA. Enzymes in the matrix degrade fatty acids
two carbons at a time in a series of oxidative reactions that yield NADH, the reduced form of flavin
adenine dinucleotide (FADH2, another energy-rich
electron carrier associated with an integral membrane enzyme complex), and acetyl-CoA for the
citric acid cycle.
Breakdown of acetyl-CoA during one turn of the
citric acid cycle produces three molecules of NADH,
333
334
SECTION VI — Cellular Organelles and Membrane Trafficking
A. Glycolysis (in the cytoplasm)
OPO32–
HOH2C
H2C
O H ATP ADP H
O H
H
H
H
HO OH H OH
HO OH H OH
Hexokinase
H
OH
Glucose
H
OH
Glucose
6-phosphate
OPO32–
O
H2C
OPO32–
OH
O
CH2 ATP ADP H2C
H H HO OH
Phosphoglucose
isomerase
OH H
Fructose
6-phosphate
H H HO OH
Phosphofructokinase
OH H
Fructose
1,6-biphosphate
NADH + H+
NAD+
COO –
HO C H
Maltate
CH2
COO –
H2O
COO –
CH
Fumarate
CH
COO –
Phosphoglycerate
kinase
2 ATP
H H O
3-phosphoglycerate H C C C O–
(2 molecules)
O OH
PO32–
H2O
COO –
CH2
cis-Aconitate C COO –
CH
COO –
Phosphoglyceromutase
H H O
2-phosphoglycerate
–
(2 molecules) H C C C O
HO OPO32–
H2O
COO –
Isocitrate CH2
H C COO –
HO C H
COO –
Enolase
2 H2O
H H O
Phosphoenolpyruvate
–
(2 molecules) H C C C O
2–
OPO3
2 ADP
Pyruvate
NAD+
kinase
CO2 + NADH + H+
FAD
CH2
Succinate
CH2
–
COO
GTP + HSCoA
GDP + Pi
COO –
CH2
α-Keto- CH2
glutarate
C O
COO –
Succinyl CoA
O SCoA
C
CH2
CH2
COO –
2 NADH + 2 H+
H H O
1,3-bisphosphoglycerate H C C C OPO32–
(2 molecules)
O OH
PO32–
2 ADP
COO –
CH2
HO C COO –
Citrate CH2
COO –
FADH2
COO –
Triosephosphate
isomerase
3-phosphate
dehydrogenase
HSCoA
COO –
C O Oxaloacetate
CH2
COO –
Aldolase
HO O H
H C C C OPO3H–
H
O
H H O
Glyceraldehyde H C C CH
3-phosphate
O OH
(2 molecules)
PO32–
2 NAD + 2 Pi
Glyceraldehyde
B. Citric acid cycle (in the mitochondrial matrix)
O
H2O + CH3 C SCoA
Acetyl CoA
Dihydroxyacetone
phosphate
OPO32–
CH2
2 ATP
H O O
Pyruvate
–
(2 molecules) H C C C O
H
C. Integration of metabolic
pathways in mitochondrium
ADP
NAD+ + HSCoA
CO2 + NADH + H+
ATP
ADP
O2 H2O + Pi ATP
H+ H+ H+
e–
FADH2
CO2
Pyruvate
Fatty acids Pyruvate
H+
Pi
O2
Glycosis
Lipid
breakdown
H+
FADH2
Acetyl CoA
Citric
acid
cycle
CO2
NADH
NADH
Figure 19-4 METABOLIC PATHWAYS SUPPLYING ENERGY FOR OXIDATIVE PHOSPHORYLATION. A, Glycolysis. B, Citric acid cycle. Production of acetylCoA by the glycolytic pathway in cytoplasm and fatty acid oxidation in the mitochondrial matrix drive the citric acid cycle in the mitochondrial
matrix. This energy-yielding cycle is also called the Krebs cycle after the biochemist H. Krebs. NADH and FADH2 produced by these pathways
supply high-energy electrons to the electron transport chain. C, Overview of metabolic pathways. Note energy-rich metabolites (yellow).
335
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
one molecule of FADH2, and two molecules of carbon
dioxide. Energetic [energiereich] electrons donated
by NADH and FADH2 drive an electron transport
pathway in the inner mitochondrial membrane that
powers a chemiosmotic cycle to produce ATP (Fig.
19-5). Electrons use two routes to pass through three
protein complexes in the inner mitochondrial membrane. Starting with NADH, electrons pass through
complex I to complex III to complex IV. Electrons
from FADH2 pass through complex II to complex III
to complex IV. Along both routes, energy is partitioned off [wird aufgeteilt] to transfer multiple protons
(at least 10 electrons per NADH oxidized) across the
Cytochrome c
H+
INTERMEMBRANOUS
SPACE
+
A
inner mitochondrial membrane from the matrix to
the inner membrane space. The resulting electrochemical gradient of protons drives ATP synthesis (see
Fig. 8-5).
This process is called oxidative phosphorylation,
since molecular oxygen is the sink [Ausguss] for energybearing electrons at the end of the pathway and since
the reactions add phosphate to ADP. Eukaryotes that live
in environments with little or no oxygen use other
acceptors for these electrons and produce nitrite, nitric
oxide [Stickstoffmonoxid], or other reduced products
rather than water. Oxidative phosphorylation is understood in remarkable detail, thanks to atomic structures
H
H+
ATP
H+
Pi
+
+ +
Q
e–
– –
+
+
+
QH2
e–
e-
+
O2
e-
–
–
–
H2O
+
–
H+
H+
+
–
–
ADP
+
+
–
–
ADP + Pi
FADH2 FAD
Succinate
Complex II
NADH NAD+
Complex I
B
Complex III
Complex IV
Complex V
Carriers
MATRIX
Rieske
protein
Cytochrome c1
ATP
Subunit II
INTERMEMBRANOUS
SPACE
F0
MATRIX
Cytochrome b
Subunit I
Subunit III
Cytochrome c oxidase
Complex III
Complex IV
F1
Complex V
Figure 19-5 CHEMIOSMOTIC CYCLE OF THE RESPIRATORY ELECTRON TRANSPORT CHAIN AND ATP SYNTHASE. A, left panel, A mitochondrion for orientation. Right panel, The electron transport system of the inner mitochondrial membrane. Note the pathway of electrons through the four
complexes (red and yellow arrows) and the sites of proton translocation between the matrix to the intermembranous space (black arrows).
The stoichiometry is not specified, but at the last step, four electrons are required to reduce oxygen to water. ATP synthase uses the electrochemical proton gradient produced by the electron transport reactions to drive ATP synthesis. B, The available atomic structures of the
electron transport chain are shown. In the cytochrome bc1 complex III, the 3 of 11 mitochondrial subunits used by bacteria are shown as
ribbon models. The supporting subunits found in mitochondria are shown as cylinders. The four subunits of complex IV encoded by the
mitochondrial genome are shown as ribbon models. They form the functional core of the complex, which is supported by additional subunits
shown as cylinders. See Figure 8-4 for further details of ATP synthase (complex V). (B, Images of complex III and complex IV courtesy of
M. Saraste, European Molecular Biology Laboratory, Heidelberg, Germany. Reference: Zhang Z, Huang L, Schulmeister VM, et al: Electron
transfer by domain movement in cytochrome bc1. Nature 392:677–684, 1998. PDB file: 1BCC. Reference: Yoshikawa S, Shinzawa-Itoh K,
Nakashima R, et al: Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase. Science 280:1723–1729, 1998. PDB
file: 2OCC.)
336
SECTION VI — Cellular Organelles and Membrane Trafficking
of ATP synthase and three of the four electron transfer
complexes. Nuclear genes encode most of the protein
subunits of these complexes, but mitochondrial genes
are responsible for a few key subunits.
Bacteria and mitochondria share homologous proteins for the key steps in oxidative phosphorylation (Fig.
19-2), but the machinery in mitochondria is usually
more complex. Thus, bacteria are useful model systems
with which to study the common mechanisms. Plasma
membranes of bacteria and inner membranes of mitochondria have equivalent components, and the bacterial
cytoplasm corresponds to the mitochondrial matrix
(Fig. 19-2).
Energy enters this pathway in the form of electrons
that are produced when NADH is oxidized to NAD + ,
releasing one H + and two electrons (Fig. 19-5). If the
proton and electrons were to combine immediately
with oxygen, their energy would be lost as heat. Instead,
these high-energy electrons are separated from the
protons and then passed along the electron transport
pathway before fi nally recombining to reduce molecular
oxygen to form water. Along the pathway, electrons
associate transiently [temporär] with a series of oxidation/reduction acceptors, generally metal ions associated with organic cofactors, such as hemes in
cytochromes and iron-sulfur centers (2Fe2S) and copper
centers in complex IV. Electrons move along the transport pathway at rates of up to 1000 s−1. To travel at this
rate through a transmembrane protein complex spanning a 35-nm lipid bilayer, at least three redox cofactors
are required in each complex, because the efficiency of
quantum mechanical tunneling of electrons between
redox cofactors falls off rapidly with distance. Two
cofactors, even with optimal orientation, would be too
slow.
Step by step, electrons give up energy as they move
along the transport pathway. In three complexes along
the pathway, this energy is used to pump protons from
the matrix to the inner membrane space. This establishes an electrochemical proton gradient across the
inner mitochondrial membrane that is used by ATP synthase to drive ATP production. Direction is provided to
the movements of electrons by progressive increases
[fortschreitende Zunahme] in the electron affinity of
the acceptors. The final acceptor, oxygen (at the end of
the pathway), has the highest affi nity.
The first component of the electron transport
pathway is called complex I (or NADH:ubiquinone oxidoreductase). Vertebrate mitochondrial complex I with
46 different protein subunits is more complex than bacterial complex I with 14 subunits. NADH donates two
electrons to flavin mononucleotide associated with
protein subunits located on the matrix side of the inner
membrane. A crystal structure of the cytoplasmic
domain of the bacterial complex shows the path for the
electrons from flavin mononucleotide through seven
iron sulfur clusters to quinone in the lipid bilayer [Dop-
pelschicht]. For each molecule of NADH oxidized, the
transmembrane domains of complex I transfer four
protons from the matrix into the inner membrane
space.
The second component of the electron transport
pathway is complex II or succinate:ubiquinone reductase, a transmembrane enzyme that makes up part of
the citric acid cycle. Complex II couples oxidation of
succinate (a four-carbon intermediate in the citric acid
cycle) to fumarate with reduction of flavin adenine dinucleotide (FAD) to FADH2. Complex II does not pump
protons but transfers electrons from FADH2 to ubiquinone. Reduced ubiquinone carries these electrons to
complex III.
The third component of the electron transport
pathway is complex III, also called cytochrome bc1.
This well-characterized, transmembrane protein complex consists of 11 different subunits. The homologous
bacterial complex has only three of these subunits,
the ones that participate in energy transduction in
mitochondria. Eight other subunits surround this core.
Complex III couples the oxidation and reduction of
ubiquinone to the transfer of protons from the matrix
across the inner mitochondrial membrane. Energy is
supplied by electrons that move through the cytochrome
b subunit to a subunit with a 2Fe2S redox center. This
subunit then rotates into position to transfer the electron to cytochrome c1, another subunit of the complex.
Cytochrome c1 then transfers the electron to the watersoluble protein cytochrome c in the intermembranous
space (or periplasm of bacteria).
Cytochrome oxidase, complex IV, takes electrons
from four cytochrome c molecules to reduce molecular
oxygen to two waters as well as to pump four protons
out of the matrix. Mitochondrial genes encode the three
subunits that form the core of this enzyme, carry out
electron transfer, and translocate protons. Nuclear genes
encode the surrounding 10 subunits.
The electrochemical proton gradient produced by
the electron transport chain provides energy to synthesize ATP. Chapter 8 explained how the rotary [rotierend] ATP synthase (complex V) can either use ATP
hydrolysis to pump protons or use the transit of protons
down an electrochemical gradient to synthesize ATP
(see Figs. 8-5 and 8-6). The proton gradient across the
inner mitochondrial membrane drives rotation of the γsubunit. The rotating γ-subunit physically changes the
conformations of the α- and β-subunits, bringing
together ADP and inorganic phosphate to make ATP. An
antiporter in the inner membrane exchanges cytoplasmic ADP for ATP synthesized in the matrix (see
Fig. 9-2A).
Mitochondria and Disease
As expected from the central role of mitochondria in
energy metabolism, mitochondrial dysfunction contrib-
337
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
utes to a remarkable diversity of human diseases (Fig.
19-6) including seizures [Krampfanfälle], strokes [Hirnschläge], optic atrophy [Sehnervenatrophie], neuropathy, myopathy, cardiomyopathy, hearing loss, and Type
2 diabetes mellitus. These disorders arise from mutations in genes for mitochondrial proteins encoded by
both mitochondrial DNA (mtDNA) and nuclear DNA.
More than half of the known disease-causing mutations
are in genes for mitochondrial transfer RNAs.
The existence of about 1000 copies of mtDNA per vertebrate cell influences the impact [Auswirkungen] of deleterious [schädlich] mutations. A mutation in one copy
would be of no consequence, but segregation of mtDNAs
may lead to cells in which mutant mtDNAs predominate,
yielding defective proteins. For example, a recurring [wiederholt auftretend] point mutation in a subunit of complex
I causes some patients to develop sudden onset of blindness in middle age owing to the death of neurons in the
optic nerve. Patients with the same mutation in a larger
fraction of mtDNA molecules suffer from muscle weakness and mental retardation [geistige Behinderung] as
children. Mutations in the genes for subunits of ATP synthase cause muscle weakness and degeneration of the
retina. Slow accumulation of mutations in mtDNA may
contribute to some symptoms of aging.
Mutations in nuclear genes for mitochondrial proteins cause similar diseases (Fig. 19-6A). A mutation in
one subunit of the protein import machinery (see Fig.
18-5), Tim8, causes a type of deafness.
Chloroplasts
Structure and Evolution of
Photosynthesis Systems
Photosynthetic Bacteria and chloroplasts of algae and
plants (Fig. 19-7) use chlorophyll to capture the remarkable amount of energy carried by single photons to
boost electrons to an excited state. These high-energy
electrons drive a chemiosmotic cycle to make NADPH
and ATP, energy currency [Währung] that is used by all
cells. Photosynthetic organisms use ATP and the reducing power of NADPH to synthesize three-carbon sugar
phosphates from carbon dioxide. Glycolytic reactions
(Fig. 19-4) running backward use this three-carbon
sugar phosphate to make six-carbon sugars and more
complex carbohydrates for use as metabolic energy
sources and structural components. Some Archaea,
such as Halobacteria halobium, and some recently discovered Bacteria use a completely different light-driven
pump lacking chlorophyll to generate a proton gradient
to synthesize ATP. Retinol associated with bacteriorhodopsin absorbs light to drive proton transport (see
Fig. 8-3).
Photosynthesis originated approximately 3.5 billion
years ago in a Bacterium, most likely a gram-negative
purple bacterium (see Fig. 2-4). These bacteria evolved
A. Disorders secondary to mutations in nuclear DNA–encoded proteins
Complex II
Complex III
Number of subunits Complex I
nDNA-encoded
~35
4
10
Leigh syndrome Leigh syndrome
Leukodystrophy Paraganglioma
SPACE
Complex IV
Complex V
10
~14
Leigh syndrome
Cardioencephalomyopathy
Leukodystrophy/tubulopathy
Cytochrome C
H+
H+
INTERMEMBRANOUS
H+
ATP
H+
Pi
+
+
–
–
Q
+
e–
+
+
+
+
–
–
–
QH2
e–
e-
O2
e-
H2O
+
–
H+
+
–
–
H+
ADP
+
+
–
–
ADP + Pi
NADH NAD+
FADH2 FAD
Succinate
ATP
B. Disorders secondary to mutations in mitochondrial DNA–encoded proteins
Complex II
Number of subunits Complex I
7
0
mtDNA-encoded
LHON
LHON + Dystonia
Sporadic myopathy
Complex III
1
Sporadic myopathy
Complex IV
3
Sporadic anemia
Sporadic myopathy
Encephalomyopathy
Complex V
2
NARP
MILS
FBSN
MATRIX
Figure 19-6 Mutations in both mitochondrial and nuclear genes for mitochondrial proteins cause a variety of diseases by compromising
[Beeinträchtigung] the function of particular mitochondrial subsystems. FBSN, familial bilateral striatal necrosis; LHON, Leber hereditary
optic neuropathy; MILS, maternally inherited Leigh syndrome; NARP, neurogenic muscle weakness, ataxia, retinitis pigmentosa. (Adapted
from Schon EA: Mitochondrial genetics and disease. Trends Biochem Sci 25:555–560, 2000.)
338
SECTION VI — Cellular Organelles and Membrane Trafficking
A
Grana
Thylakoid
space
Thylakoid
membrane
Stroma
Outer membrane
Inner membrane
B. Chloroplast
Outer membrane
Inner membrane
Stroma
Thylakoid
space
Thylakoid
membrane
Grana
Grana
Starch granule
DNA
Ribosomes
C
THYLAKOID SPACE
STROMA
D
PERIPLASM
CYTOPLASM
E. Cyanobacterium
Cell wall
Plasma
membrane
Thylakoid
membrane
Thylakoid
space
Cytoplasm
DNA
Ribosomes
Figure 19-7 MORPHOLOGY OF CHLOROPLASTS AND CYANOBACTERIA.
A, Electron micrograph of a thin section of a spinach chloroplast.
B, Chloroplast. C–D, Comparison of the machinery in the photosynthetic membranes of chloroplasts and cyanobacteria. E, Drawing of
a cyanobacterium illustrating the internal folds of the plasma membrane to form photosynthetic thylakoids. (A, Courtesy of K. Miller,
Brown University, Providence, Rhode Island.)
components to assemble a transmembrane complex of
proteins, pigments, and oxidation/reduction cofactors
called a reaction center (Fig. 19-8). Reaction centers
absorb light and initiate an electron transport pathway
that pumps protons out of the cell. Such photosystems
turn sunlight into electrical and chemical energy with
40% efficiency, better than any human-made photovoltaic cell. Given their alarming complexity and physical
perfection, it is remarkable that photosystems emerged
only a few hundred million years after the origin of life
itself.
Broadly speaking, photosynthetic reaction centers of
contemporary organisms can be divided into two different groups (Fig. 19-8). The reaction centers of purple
bacteria and green fi lamentous bacteria utilize the
pigment pheophytin and a quinone as the electron
acceptor, similar to photosystem II of cyanobacteria
and chloroplasts. The reaction centers of green sulfur
bacteria and heliobacteria have iron-sulfur centers as
electron acceptors, similar to photosystem I of cyanobacteria and chloroplasts.
Cyanobacteria are unique among Bacteria in that
they have both types of photosystems as well as a
manganese [Mangan] enzyme that splits water, releasing
from two water molecules four electrons, four protons,
and oxygen (Fig. 19-7E). Coupling this enzyme to photosynthesis was a pivotal [entscheidend] event in the
history of the earth, as this reaction is the source of
most of the oxygen in the earth’s atmosphere.
Chloroplasts of eukaryotic cells arose from a symbiotic cyanobacterium (see Fig. 2-8). Much evidence
indicates that this event occurred just once, giving
all chloroplasts a common origin. However, to account
for chloroplasts in organisms that diverged prior to
the acquisition of chloroplasts, one must also postulate
lateral transfer of chloroplasts from, for example, a
green alga to Euglena. Less likely, but not ruled out
conclusively, cyanobacteria may have colonized eukaryotic cells on up to three different occasions, giving rise
to organelles that evolved into chloroplasts.
Chloroplasts have retained [behalten] up to 250 original bacterial genes on circular genomes, whereas many
bacterial genes were lost or moved to the nucleus of
host eukaryotes. Chloroplast genomes encode subunits
of many proteins responsible for photosynthesis and
chloroplast division, ribosomal RNAs and proteins, and
a complete set of tRNAs. Chloroplast proteins encoded
by nuclear genes are transported posttranslationally
into chloroplasts (Fig. 18-6) after their synthesis in
cytoplasm.
The organization of cyanobacterial membranes explains the architecture of chloroplasts (Fig. 19-7C–E).
In cyanobacteria, light-absorbing pigments, as well as
protein complexes involved with electron transport and
ATP synthesis, are concentrated in invaginations of the
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
A. Purple bacteria, green filamentous bacteria
PERIPLASM
-1.0
H+
3 H+
+
QB
e-
QH2
ADP
+ Pi
H+
Light
PERIPLASM
H+
Light
Fes
Fes
Purple bacteria
D. Electron energy
BChl2*
– –
NAD
reductase
ATP synthase
0
BChl2
0.5
Green sulfur bacteria
F. Electron energy
LUMEN
Plastocyanin
Chl2*
H+
-1.0
+
Fes
H+
Fes
2 H+
H
Light-harvesting
complexes
FX
FA/B
NAD
-0.5
CYTOPLASM
e-
QH2
Chl
1.0
Light
e-
BChl2
+ +
PERIPLASM/
Light Mn2+
QB
QB
Cytochrome bc1
Cytochrome c2
ATP
E. Cyanobacteria, algae, plants
QA
0.5
ADP
+ Pi
eNAD NADH
+ H+
Cytochrome bc
Type I
complex
photosystem
H+
–
H+
Ferridoxin
2
QA
0
-1.0
Light-harvesting complex
2 H2O
BChl
BPhe
1.0
H+
3 H+
-0.5
ATP synthase
CYTOPLASM
+
4 H+ + O
BChl2*
ATP
C. Green sulfur bacteria Heliobacteria
Cytochrome c2
H+
– –
–
2 H+
H
Light-harvesting
complex
Type II
Cytochrome bc1
photosystem
complex
+ +
eFerridoxin
Photosystem II Cytochrome b6-f Photosystem I
complex
NADP NADPH
+ H+
NADP
reductase
H+
+ +
– –
–
ADP
+ Pi
ATP
ATP synthase
STROMA/
CYTOPLASM
Energy (volts)
QA
H+
Energy (volts)
Light
B. Electron energy
Cytochrome c2
Energy (volts)
Cytochrome
Chl2*
-0.5
QA
QB
0.5
H2O
1.0
FX
FA/B
NAD
Phe
0
Chl2
Chl
Q
Chl2
YZ
Chloroplasts and cyanobacteria
Photosystem II
Photosystem I
Figure 19-8 COMPARISON OF PHOTOSYNTHETIC COMPONENTS, ELECTRON TRANSPORT PATHWAYS, AND CHEMIOSMOTIC CYCLES TO MAKE ATP. A–B, Type
II photosystem only. C–D, Type I photosystem only. E–F, Both photosystem II and photosystem I. Right diagrams, The energy levels of electrons in the three types of photosynthetic organisms, showing excitation of an electron by an absorbed photon (vertical arrows), electron
transfer pathways through each reaction center (arrows sloping right), and electron transfer steps outside the reaction centers (arrows sloping
left). (A, C, and E, Reference: Kramer DM, Schoepp B, Liebl U, Nitschke W: Cyclic electron transfer in Heliobacillus mobilis. Biochemistry
36:4203–4211, 1997. B, D, and F, Reference: Allen JP, Williams JC: Photosynthetic reaction centers. FEBS Lett 438:5–9, 1998.)
plasma membrane. The F1 domain of ATP synthase faces
the cytoplasm, and the lumen of this membrane system
is periplasmic. This internal membrane system remains
in chloroplasts but is separated from the inner membrane (the former plasma membrane). These thylakoid
membranes contain photosynthetic hardware and
enclose the thylakoid membrane space. Like the bacterial plasma membrane, the chloroplast “inner membrane” is a permeability barrier, containing carriers
for metabolites. The inner membrane surrounds the
339
340
SECTION VI — Cellular Organelles and Membrane Trafficking
stroma, the cytoplasm of the original symbiotic bacterium, a protein-rich compartment devoted to synthesis
of three-carbon sugar phosphates, chloroplast proteins,
and all plant fatty acids. The stroma also houses the
genomes and stores starch [Stärke]. The outer membrane, like the comparable bacterial and mitochondrial
membranes, has large pore channels that allow free
passage of metabolites.
Light and Dark Reactions
Photosynthetic mechanisms capture energy from
photons to drive two types of reactions:
• Light reactions depend on continuous absorption of photons. These reactions occur in or on the
surface of thylakoid membranes. They include
generation of high-energy electrons, electron
transport to make NADPH, creation of a proton
gradient across the thylakoid membrane for the
chemiosmotic synthesis of ATP, and generation of
oxygen.
• Dark reactions convert carbon dioxide into threecarbon sugar phosphates. These reactions continue
for some time in the dark. However, they depend
on ATP and NADPH produced by light reactions,
so they eventually stop when ATP and NADPH are
exhausted in the dark. These reactions account for
most of the carbon dioxide converted to carbohydrates on earth. (Alternatively specialized prokaryotes drive carbon fi xation by oxidation of hydrogen
sulfide and other inorganic compounds.)
All photosynthetic systems use similar mechanisms
to capture energy from photons (Fig. 19-8). Pigments
associated with transmembrane proteins in photosynthetic reaction centers absorb photons and use the
energy to boost electrons to a high-energy, excited
state. Subsequent electron transfer reactions partition
this energy in several steps to generate a proton gradient across the membrane. Generation of this proton
electrochemical gradient and chemiosmotic production of ATP are similar to oxidative phosphorylation
(Fig. 19-5).
Specific photosynthetic systems differ in the complexity of the hardware, the source of electrons, and
the products (Fig. 19-8). Most photosynthetic bacteria
use either a type I photosystem or a type II photosystem to create a proton gradient to synthesize ATP.
Cyanobacteria and green plants use both types of
reaction centers in series to raise electrons to an
energy sufficient to make NADPH in addition to ATP.
These advanced systems also use water as the electron donor and produce molecular oxygen as a byproduct.
Energy Capture and Transduction
by Type II Photosystems and
Photosystem II
The reaction center from the purple bacterium Rhodopseudomonas viridis (Fig. 19-9A) is a model for the
more complex photosystem II of cyanobacteria and
chloroplasts. This bacterial reaction center consists of
just four subunits. A cytochrome subunit on the periplasmic side of the membrane donates electrons. Two
core subunits form a rigid [starr] transmembrane framework to bind 10 cofactors in orientations that favor
transfer of high-energy electrons from two “special”
bacteriochlorophylls through chlorophyll b and
bacteriopheophytin b.
Photosynthesis begins with absorption of a photon
by the special pair bacteriochlorophylls. Photons in
the visible part of the spectrum are quite energetic
[energiereich], 40 to 80 kcal mol−1, enough to make
several ATPs. The purple bacterium reaction center
absorbs relatively low-energy, 870-nm red light. The
energy elevates an electron in the special pair bacteriochlorophylls to an excited state (Fig. 19-8B). In an
organic solvent, the excited state would decay
[abnehmen] rapidly (109 s −1), and the energy would
dissipate [vergeuden] as heat or emission of a less energetic photon by fluorescence or phosphorescence.
However, reaction centers are optimized to transfer
excited-state electrons rapidly and efficiently from the
special pair bacteriochlorophylls to bacteriopheophytin (3 × 10−12 s) and then to tightly bound quinone A
(200 × 10−12 s). Transfer is by quantum mechanical
tunneling right through the protein molecule. Because the tunneling rate falls off quickly with distance,
four redox centers must be spaced close together to
allow an energetic electron to transfer across the lipid
bilayer faster than spontaneous decay of the excited
state.
On the cytoplasmic side of the membrane, two electrons transfer from quinone A to loosely bound quinone
B (100 × 10−9 s), where they combine with two protons
to make a high-energy reduced quinone, QH2 (Fig.
19-8A). In purple bacteria, these cytoplasmic protons
are taken up through water-filled channels in the reaction center, contributing to the proton gradient.
QH2 has a low affinity for the reaction center and
diffuses in the hydrophobic core of the bilayer to
the next component in the pathway, the chloroplast
equivalent of the mitochondrial cytochrome bc1 complex
III (Fig. 19-8A). As in mitochondria, passage of energetic
electrons through this complex releases protons from
QH2 on the periplasmic side of the membrane, adding
to the electrochemical gradient. The electron circuit is
completed by transfer of low-energy electrons from
complex bc1 to a soluble periplasmic protein, cytochrome c2. Electrons then move to the cytochrome
subunit of the reaction center, which supplies special
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
A. Purple bacterium type II photosystem
reaction center
B. Cyanobacterium type I
photosystem
Cytochrome
Hemes
L
Electron
pathway
PsaM
PsaA/B
PsaK
PsaF/J
Clb
eC1
Car
eC2
eC3
Phb
QB
Fe
QA
M
FX
PsaE
PsaL/I
PsaD
H
PsaC
CYTOPLASM
Figure 19-9 STRUCTURES OF PHOTOSYSTEM HARDWARE. A, Ribbon diagram of type II photosystem from the purple bacterium Rhodopseudomonas viridis, with ball and stick models of bacteriochlorophyll and other cofactors to the right in their natural orientations. Similar core
subunits L and M each consists of five transmembrane helices. This pair of subunits binds four molecules of chlorophyll b (Clb), two molecules of bacteriopheophytin b (Phb), one nonheme iron (Fe), two quinones (QA, QB), and one carotenoid (Car) in a rigid framework. A cytochrome with four heme groups binds to the periplasmic side of the core subunits. Subunit H associates with the core subunits via one
transmembrane helix and with their cytoplasmic surfaces. The atomic structure of this photosynthetic reaction center was the Nobel Prize
work of J. Deisenhoffer, R. Huber, and H. Michel. B, Ribbon diagram of photosystem I of Synechococcus elongatus, with ball and stick
models of chlorophyll and other cofactors to the right in their natural orientations. This trimeric complex consists of three identical units,
each composed of 11 polypeptide chains. Within each of these units, this 4-Å resolution structure includes 43 α-helices, 89 chlorophylls,
a quinone, and three iron-sulfur centers, but other details (e.g., amino acid side chains) are not resolved. The photosynthetic reaction
center consists of the C-terminal halves of the two central subunits (PsaA/PsaB, red-brown) associated with six chlorophylls, one or two
quinones, and a shared iron-sulfur cluster. Plastocyanin or cytochrome c6 on the lumen side donates electrons to reduce the P700 special
pair chlorophylls (eC1) of the reaction center. Light energizes an electron, which passes successively through two other chlorophylls, a
quinone, and the shared iron-sulfur cluster (red), Fx. The electron then transfers to the iron-sulfur clusters of the accessory subunit PsaC
on the stromal side of the membrane. The surrounding eight subunits (red, gray), associated with about 80 chlorophylls, compose the core
antenna system, forming a nearly continuous ring of α-helices around the reaction center. Absorption of light by additional light-harvesting
complexes [Lichtsammelkomplexe] and these antenna subunits puts chloroplast electrons into an excited state. This energy passes from
one pigment to the next until it eventually reaches the reaction center. (A, Copyright of Deisenhoffer & Michel, Nobel Foundation, 1988.
Reference: Deisenhoffer J, Michel H: The photosynthetic reaction center from the purple bacterium Rhodopseudomonas viridis. Science
245:1463–1473, 1989. PDB file: 1PRC. A 3.5 Å crystal structure [PDB file: 1IZL] of the PSII complex from the cyanobacterium Thermosynechococcus elongatus including 19 subunits is now available. Reference: Ferreira KN, Iverson TM, Maghlaoui K, et al: Architecture of
the photosynthetic oxygen-evolving center. Science 303:1831–1838, 2004. B, PDB file: 2PPS. Reference: Schubert W-D, Klukas O, Krauss
N, et al: Photosystem I of Synechococcus elongatus at 4 Å resolution: Comprehensive structure analysis. J Mol Biol 272:741–769, 1997.)
pair chlorophylls with electrons for the photosynthetic
reaction cycle.
The net result of this cycle is the conversion of
the energy of two photons into transport of three
protons to the periplasm. A diagram of the energy levels
of the various intermediates in the cycle (Fig. 19-8B)
shows how energy is partitioned after an electron is
excited by a photon and then moves, step by step,
through protein-associated redox centers back to the
ground state.
The proton electrochemical gradient established by
photosynthetic electron transfer reactions is used to
drive an ATP synthase (see Fig. 8-5) similar to those of
nonphotosynthetic prokaryotes and mitochondria.
Light Harvesting
Reaction center chlorophylls absorb light themselves,
but both chloroplasts and bacteria increase the efficiency of light collection with proteins that absorb light
341
342
SECTION VI — Cellular Organelles and Membrane Trafficking
and transfer the energy to a reaction center. Most of
these light-harvesting complexes are small, transmembrane proteins that cluster around a reaction center,
although some bacteria and algae also have soluble lightharvesting proteins. Transmembrane, light-harvesting
proteins consist of a few α-helices associated with multiple chlorophyll and carotenoid pigments (Figs. 19-8A
and C and 19-9B). The use of different pigments broadens the range of wavelengths absorbed. Multiple pigments increase the efficiency of photon capture. Leaves
are green because chlorophylls and carotenoids absorb
purple and blue wavelengths (<530 nm) as well as red
wavelengths (>620 nm), reflecting only yellow-green
wavelengths in between.
Light that is absorbed by light-harvesting proteins
boosts pigment electrons to an excited state. This
energy (but not the electrons) moves without dissipation [Verlust] by fluorescence resonance energy
transfer from one closely spaced pigment molecule to
another and eventually to the special pair chlorophylls
of a reaction center. This rapid (10−12 s), efficient process
transfers energy captured over a wide area to a reaction
center to initiate a cycle of electron transfer and energy
transduction.
Energy Capture and Transduction by
Photosystem I
The reaction centers of green sulfur bacteria and heliobacteria are similar to photosystem I of cyanobacteria
and chloroplasts. Generation of a proton gradient by
photosystem I has many parallels with photosystem II.
Direct absorption of light or resonance energy transfer
from surrounding light-harvesting complexes excites
special pair chlorophylls in photosystem I (Fig. 19-8C–
D). Excited-state electrons move rapidly within the
reaction center from these chlorophylls through two
accessory chlorophylls and to an iron-sulfur center.
The pathway includes a quinone in cyanobacteria and
chloroplasts. Electrons then move to the iron-sulfur
center of a subunit on the cytoplasmic side of the membrane. The subsequent events in green sulfur bacteria
and heliobacteria are still under investigation but are
thought to include electron transfer by the soluble
protein ferridoxin to an NAD reductase, followed by
transfer by a lipid intermediate to cytochrome bc
complex, and then back to the reaction center via a
cytochrome c.
Oxygen-Producing Synthesis of NADPH
and ATP by Dual Photosystems
Chloroplasts and cyanobacteria combine photosystem
II and photosystem I in the same membrane to form a
system capable of accepting low-energy electrons from
the oxidation of water and producing both a proton
gradient to drive ATP synthesis and reducing equiva-
lents in the form of NADPH (Fig. 19-8E–F). Both photosystems are more elaborate in dual systems than in
single systems. Although plant photosystem II, with
more than 25 protein subunits, is much more complicated than is the homologous reaction center of purple
bacteria, the arrangement of transmembrane helices
and chlorophyll cofactors in the core of the plant reaction center is similar to the simple reaction center of
purple bacteria.
Photosynthesis involves a tortuous [gewunden] electron transfer pathway powered at two way stations by
absorption of photons. This process begins when the
special pair chlorophylls of photosystem II are excited
by direct absorption of light or by resonance energy
transfer from surrounding light-harvesting complexes
(Fig. 19-8E–F). Electrons come from splitting two waters
into molecular oxygen and four protons. Excited-state
electrons tunnel through the redox cofactors and
combine with protons from the stroma (or cytoplasm in
bacteria) to reduce quinone QB to QH2, a high-energy
electron donor. QH2 diffuses to complex b6-f, the chloroplast equivalent of the mitochondrial bc1 complex.
Passage of electrons through complex b6-f releases
protons from QH2 into the thylakoid lumen (or bacterial
periplasm), contributing to the proton gradient across
the membrane.
Complex b6-f donates [abgeben] electrons from QH2
to photosystem I. Direct absorption of 680-nm light or
resonance energy transfer from surrounding light-harvesting complexes boosts special pair chlorophyll electrons to a very high-energy, excited state (Fig. 19-8F).
Excited-state electrons pass through chlorophyll and
iron-sulfur centers of photosystem I to the iron-sulfur
center of the redox protein, ferridoxin, on the cytoplasmic/stromal surface of the membrane. The enzyme
NADP reductase combines electrons from ferridoxin
with a proton to form NADPH, the final product of this
tortuous electron transfer pathway powered at two way
stations by absorption of photons. Uptake of stromal
protons during NADPH formation contributes to the
transmembrane proton gradient for the synthesis of
ATP. Antiporters in the inner membrane exchange ATP
for ADP, as in mitochondria.
Synthesis of Carbohydrates
ATP and NADPH produced by light reactions drive
the unfavorable conversion of carbon dioxide into
sugars. This is the first step in the earth’s annual production of about 1010 tons of carbohydrates by photosynthetic organisms. This process is very expensive,
consuming three ATPs and two NADPHs for each
carbon dioxide added to the five-carbon sugar ribulose
1,5-bisphosphate. The responsible enzyme, ribulose
phosphate carboxylase (called RUBISCO), is the
most abundant protein in the stroma and might be the
CHAPTER 19 — Mitochondria, Chloroplasts, Peroxisomes
most abundant protein on the earth. The products
of combining the five-carbon sugar with carbon
dioxide are two molecules of the three-carbon sugar
3-phosphoglycerate.
An antiporter in the inner chloroplast membrane
exchanges 3-phosphoglycerate for inorganic phosphate,
so 3-phosphoglycerate can join the glycolytic pathway
in the cytoplasm (Fig. 19-4). Driven by this abundant
supply of 3-phosphoglycerate, the glycolytic pathway
runs backward to make six-carbon sugars, which are
used to make disaccharides such as sucrose [Saccharose] to nourish [mit Nährstoff versorgen] nonphotosynthetic parts of the plant, the glucose polymer starch
to store carbohydrate, and cellulose for the extracellular matrix (see Figs. 3-25A and 32-12).
Peroxisomes
Peroxisomes are organelles bounded by a single membrane (Fig. 19-10), named for their content of enzymes
that produce and degrade hydrogen peroxide, H2O2.
Oxidases produce H2O2 and peroxidases such as catalase break it down. Peroxisomes also contain diverse
enzymes for the metabolism of lipids and other metabolites, including the β-oxidation of fatty acids and oxidation of bile acids [Abschnüren] and cholesterol.
Peroxisomes lack nucleic acids, and there is no evidence
that they arose from a bacterial ancestor. All peroxisomal proteins are encoded by nuclear genes, translated
on cytoplasmic ribosomes, and then subsequently incorporated into peroxisomes (see Fig. 18-8).
Peroxisomes form in two different ways: de novo
synthesis by budding from the endoplasmic reticulum
and growth and division of preexisting peroxisomes
(see Fig. 18-8). Cells that lack preexisting peroxisomes
can form peroxisomes without a template by differentiation and budding of ER membranes. PEX3 and PEX16
target to the ER, where they recruit other peroxins to
form a specialized domain that pinches off [schürt sich
ab] to form a nascent peroxisome. In addition to arising
by outgrowth from the ER, new peroxisomes can form
by fission [Teilung] of preexisting peroxisomes.
Defects in peroxisomal biogenesis cause a spectrum
of lethal human diseases known as the peroxisomal
biogenesis disorders (see Appendix 18-1). These diseases include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum’s disease, and rhizomelic
chondrodysplasia punctata. They are moderately rare,
occurring in approximately 1 in 50,000 live births. Most
patients with peroxisomal biogenesis disorders display
no defect in peroxisome membrane synthesis or import
of peroxisomal membrane proteins, but they do have
mild-to-severe defects in matrix protein import.
However, in rare cases, patients lack peroxisome membranes altogether. Studies of both yeast pex mutants and
cells from patients with peroxisomal biogenesis disor-
A
B
Figure 19-10 PEROXISOMES. A, Fluorescence micrographs of a CV1
cell expressing green fluorescent protein fused to PTS1, which
labels peroxisomes green. Microtubules are stained red with labeled
antibodies, and nuclear DNA is stained blue with propidium iodide.
B, Electron micrograph of a thin section of a tissue culture cell
showing three peroxisomes. Peroxisomes have a single bilayer
membrane and a dense matrix, including a crystal (in some species)
of the enzyme urate oxidase. (A, Courtesy of S. Subramani, University of California, San Diego. Reference: Wiemer EAC, Wenzel T,
Deernick TJ, et al: Visualization of the peroxisomal compartment in
living mammalian cells. J Cell Biol 136:71–80, 1997. B, Courtesy
of Don W. Fawcett, Harvard Medical School, Boston, Massachusetts.)
ders have provided clues regarding peroxisome biogenesis (see Fig. 18-7).
ACKNOWLEDGMENT
Thanks go to Gary Brudvig for his suggestions on revisions to
this chapter.
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