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Chapter 6
Mitochondria and Energy Conversion
The sun is the ultimate source of
energy all organisms and cells
ATP- “the free-energy currency”
– Every day, we build bones,
move muscles, think, and
perform many other activities
with our bodies. All of these
activities are based upon
energy .
– ATP: The Perfect Energy
Currency for the Cell
?
Mitochondriathe power plants of ATP
• Mitochondria are double layer membrane-enclosed
organelles distributed through the cytosol of most
eukaryotic cells. Their main function is the conversion of
the potential energy of food molecules into ATP. So
mitochondria are also called “the powerhouse” of the cell.
• In addition to supplying cellular energy, mitochondria are
involved in cell death, as well as the control of the cell cycle
and cell growth.
Outline of Mitochondria
 Brief History of Mitochondria studies
 Mitochondrial morphology and Structure
 Cellular respiration and Energy Conversion
 Mitochondria and cell death
 Mitochondria and diseases
Brief History of Mitochondria studies
• Richard Altmannin 1894, established them as cell organelles and
called them "bioblasts".
• The term "mitochondria" was coined by Carl Benda in 1898.
• Leonor Michaelis discovered Janus green can be used as a supravital
stain for mitochondria in 1900.
• In 1913 particles from extracts of guinea-pig liver were linked to
respiration by Otto Heinrich Warburg, which he called "grana".
• The first high resolution micrographs appeared in 1952, replacing the
Janus Green stains .
• The popular term "powerhouse of the cell" was coined by Philip
Siekevitz in 1957.
Mitochondrial Morphology and Structure
I. Shape, size & number
• Mitochondria are often flexible, rod-shaped organelles that are
about 0.5 to 1μm in girth and as much as 7 μ m in length.
Mitochondria vary considerably in size & shape.
• Their number correlate with the metabolic activities of the cell.
II Ultrostructure and
Functional Localization
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1. Outer membrane
2. Inner membrane
3. Inter membrane space
4. Translocation contact site
5.Matrix
6. Cristae
II Ultrostructure and
Functional Localization
II Ultrostructure and
Functional Localization
• 1. Outer membrane
• contains many complexes of integral membrane proteins
that form channels through which a variety of molecules
and ions move in and out of the mitochondrion. we called
it porins. These porins form channels that allow
molecules 5000 Daltons or less in molecular weight to
freely diffuse from one side of the membrane to the other.
2.Inner membrane
• The inner membrane, which encloses the matrix space, is
folded to form cristae. The area of the inner membrane
is about five times as great as the outer membrane.
• This membrane is richly endowed with cardiolipin, a
phospholipid that possesses four, rather than the usual
two, fatty acyl chains. The presence of this phospholipid
in high concentration makes the inner membrane nearly
impermeable to ions, electrons, and protons.
• The inner membrane has a very high protein-tophospholipid ratio (about 4:1 by weight).
• Impermeable to most charged molecules
Inner membrane contains three major types
of proteins:
• ① those that carry out the oxidation
reactions of the respiratory chain
• NADH dehydrogenase
• Cytochrome b-c1
• Cytochrome oxidase
• ② ATP synthetase
• ③ specific transport proteins
• 3. Inter membrane space
• contains several enzymes that use the ATP that passes out of
the matrix to phosphorylate other nucleotides.
• 4. Translocation contact site
• TOM(Translocon of the outer membrane)
• TIM(Translocon of the inner membrane)
• 5. Matrix
• contains hundreds of different enzymes including
those required for
• ①the oxidation of pyruvate and fatty acids
• ②the citric acid cycle.
• It also contains small amounts of mitochordrial DNA
genome, special mitochondrial ribosomes, tRNAs
and various enzymes that required for the
expression of the mitochondrial genes.
Chemical composition:
• The outer membrane consists of 40% lipids and 60 percent
proteins.
• The inner membrane is made up of 20% lipids and 80%
proteins. The electron transport enzymes, proton secreting
proteins are virtually buried in the core of the inner
membranes.
• Mitochondrial matrix also consists of a wide variety of
enzymes. There are more than 120 kinds of enzymes of
mitochondrial.
• Mitochondrial matrix also contains DNA, RNA molecules.
The mitochondrial genome
• The human mitochondrion contains 5-10 identical molecules
of DNA. Mitochondrial DNA(mtDNA) are circular, doublestranded structures of molecules in higher eukaryotes. They
encode their own mRNA, rRNA and ribosomal proteins, tRNAs
and a few mitochondrial proteins.
• Each mitochondrion consists of 16’569 base pairs carrying the
information for 37 genes.
• but only 13 of these code for polypeptides, the remainder
being the 2 ribosomal subunits and 22 types of transfer RNA.
• However, most of the proteins in the mitochondrion are
encoded in nucleus by nuclear DNA, synthesized in cytosol,
and subsequently transported into the mitochondrion.
• Because the growth and proliferation of
mitochondria are controlled by both nuclear
genome and it’s own genome. Mitochondria
are usually called semiautonomous organelle.
The transport protein into
Mitochondria
• Mitochondrial proteins are first fully synthesized
as precursor proteins in the cytosol and then
translocated into mitochondria by a
posttranslational mechanism.
1. Translocation into the Mitochondrial Matrix Depends on a
Signal Sequence and Protein Translocators
2. Mitochondrial Precursor Proteins Are Imported as
Unfolded Polypeptide Chains.
• Mitochondrial precursor proteins do not fold into their native
structures after they are synthesized; instead, they remain
unfolded through interactions with other proteins in the
cytosol(hsp70).
3. Mitochondrial Proteins Are Imported into the Matrix at
Contact Sites That Join the Inner and Outer Membranes
N-terminal signal sequence is recognized by receptors of TOM;
The protein is translocated across both Mit membranes at or near
special contact sites.
ATP Hydrolysis and a H+ Gradient are Used to Drive
Protein Import into Mitochondria.
Proper folding ensure the maturation of Mitochondria
proteins.
After the initial interaction with mitochondrial hsp70, many imported
proteins are passed on to another chaperone protein, mitochondrial
hsp60 that facilitates its folding by binding and releasing it through
cycles of ATP hydrolysis.
Protein Transport into the Inner Mitochondrial
Membrane and the Intermembrane Space Requires Two
Signal Sequences
Origin and replication of mitochondria
• Origin of mitochondria
• Many of the features of the mitochondrial genetic
system resemble those found in prokaryotes like
bacteria. This has strengthened the theory that
mitochondria are the evolutionary descendants of a
prokaryote that established an endo-symbiotic
relationship with the ancestors of eukaryotic cells
early in the history of life on earth.
Mitochondria replication
• Mitochondria replication much like bacterial
cells. When they get too large, they undergo
fission. This involves a furrowing of the inner
and then the outer membrane as if someone
was pinching the mitochondrion. Then the
two daughter mitochondria split.
II Cellular respiration and Energy
Conversion
• 1. Cellular respiration
• Cellular respiration is the process of oxidizing food
molecules to carbon dioxide and water. The energy
released is trapped in the form of ATP for use by all
the energy-consuming activities of the cell.
• The process occurs in two phases:
Glycolysis: the breakdown of glucose to pyruvic acid
oxidation of pyruvic acid to carbon dioxide and
water
Pathway of oxidation
• I: Glycolysis
• The series of reaction by which 1 molecule of
glucose is converted to 2 molecule of pyruvic
acid
• Yield: 2 ATP+ 2NADH2
• Characteristics:
• Does not require oxygen
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Takes place in cytosol
• II: Conversion of pyruvic acid to acetyl CoA.
• 2 pyruvic acid
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2 acetyl CoA (coenzyme A)
Yield: 2 NADH2
• takes place in matrix of mitochondria
• III: Citric Acid Cycle( Krebs cycle, TCA cycle).
Characteristics:
• Requires the presence of Oxygen (aerobic)
• takes place in the inner membrane of the
mitochondria.
• 2FADH2+ 6NADH2+ 2 ATP
• The electrons of NADH and FADH2 are transferred to the
respiratory chain
1ATP
• IV: Electron transport system and oxidative
phosphorylation
• The electron (hydrogen) transport chain is the
final pathway for all electrons removed from
substrate molecules during oxidation; consists
mainly of enzymes of the cytochrome group.
Molecular basis of oxidative phosphorylation:
A The Respiratory Chain
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The respiratory chain consists of 3 complexes
of integral membrane proteins
 the NADH dehydrogenase complex
 the cytochrome c reductase complex
 the cytochrome c oxidase complex
• and two freely-diffusible molecules
 ubiquinone (coenzyme Q)
 cytochrome c
• that shuttle electrons from one complex to the
next.
Molecular basis of oxidative phosphorylation:
B. ATP synthase
 The structure of the ATP synthase
F1 particle is the catalytic subunit;
The F0 particle attaches to F1 and is
embedded in the inner membrane.
F1: 5 subunits in
the ratio
3:3:1:1:1
F0: 1a：2b：12c
 Proton translocation through F0 drives ATP synthesis
by F1: Binding Change Model and rotational catalysis
Boyer proposed in
1979
Electron-transport and oxidative
phosphorylation
C. Mitchell’s Chemiosmotic theory
NADH and FADH2 carry protons (H+) and electrons (e-) to the electron transport
chain located in the membrane.
The respiratory enzyme complexes couple the energetically favorable transport of
electrons to the pumping of H+ out of the matrix and creates an electrochemical gradient
or proton motive force.
As the accumulating protons follow the electrochemical gradient back across the
membrane through an ATP synthase complex, the movement of the protons (proton
motive force) provides energy for synthesizing ATP from ADP and phosphate.
Summary
of glucose Oxidation.
• Oxidative phosphorylation is the mechanism by which the
free energy of electron is used to convert ADP to ATP :
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Each pair of electron in NADH2 generates 3 ATP
Each pair of electron in FADH2 generates 2 ATP
(1) Glycolysis:
2*2H 2NADH2,each yielding 3ATP(total:6ATP)
(2) Oxidation of pyruvic acid to acetyl CoA
2*2H 2NADH2,each yielding 3ATP (total: 6ATP)
(3)Oxidation of acetyle COA in Citric acid cycle.
– 2*2H
2FADH2,each yielding 2ATP
– 6*2H
6NADH2,each yielding 3ATP
– (total: 22ATP)
• The total yield of ATP is 34 ATP, about 90% of all the
ATP generated by the oxidation of 1 glucose.
Thus the complete oxidation of 1 glucose generates a
grand total of 38 ATP (adding 2ATP produced directly
during glycolysis and 2ATP during TCA cycle).
• Glucose + 6 O2
6 CO2 +6H2O +38ATP+heat
Mitochondria and Apoptosis
• Induction phase
• Effector phase
• Degradation phase
Xiaodong Wang, Ph.D
Mitochondrial Disease
Mitochondrial diseases are the result of either inherited or
spontaneous mutations in mtDNA or nDNA which lead to
altered functions of the proteins or RNA molecules in
mitochondria.
mtDNA mutation
Mitochondrial dysfunction
Mitochondrial-based diseases
Characteristics of mitochondrial disease
 Mitochondrial mutations have a high ratio.
 maternal inheritance
 Thresholel effect
• 1 diseases caused by mtDNA mutation
– Leber hereditary optic neuropathy
– Parkinson’s diseases
Parkinson’s Disease
• Named after English doctor James Parkinson
• Affects 1-2% of individuals over 60 years old
• Motor syndrome
• Akinesia失去活动能力
• Rigidity僵硬
• Tremor震颤
• imbalance
Summary