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Transcript
Depat.Anat.
Cytology
Dr.sarab H.
Mitochondria
Mitochondria are the “power-house” of the cells. They perform oxidative phosphorylation
for production of energy and able to synthesize lipid. Mitochondria are able to multiply; they
possess their own DNA for self-replication.
(oxidative phosphorylation is means ATP synthesis by phosphorylation of ADP is coupled
to redox (reduced and oxidized) reactions in electron transport chain, the entire aerobic
respiration process).
General features
They are rod-shaped organelle ranges from 2 to 6 μm in length and about 0.2 μm in width.
Their size is nearly equal to that of the bacterial cell.
1- It is the source of energy for cellular activities. Via oxidative phosphorylation they
produce ATP molecules (storage form of energy).
2- By electron microscope mitochondria are divided into two types: Cristae- type and
tubular- type .
3- Number of mitochondria increases or decreases within the cell according to the cellular
activity; their number increases in highly active liver and muscle cell. There are about
2000 mitochondria in hepatocyte.
4- Mitochondria are self-replicating organelles. They can grow and divide because they have
a circular molecule of DNA.
5- Their mutation can lead to diseases such as:
6- Young-adult blindness.
7- Progressive muscular disorders.
8- Some cases of Alzheimer’s disease.
9- Type -two diabetes mellitus.
Structure of mitochondria
Under light microscopic they appear as rods or filaments in cytoplasm.
By the electron microscope mitochondrion is a double membrane bound organelle formed of
:
1. Smooth outer membrane.
2. Folded inner membrane. The folds form cristae and tubules.
3. Intermembrane space (10 – 20 nm)
4. Matrix that part enclosed by the inner membrane (intercristal space).
Outer Mitochondrial Membrane
It is smooth and separated from inner membrane by
Intermembrane space. Contact sites formed of carrier proteins
between inner and outer membranes which act as pathway for
proteins and small molecules from cytoplasm into the matrix.
1
Inner Mitochondrial Membrane
It is characterized by presence of large number of porins; a channel protein permeable to
ions and metabolites that are required by mitochondria. It carries proteins that are responsible
for lipid formation.
1- It contains complexes - I, II, III, IV, V. which carry out oxidative phosphorylation which
in turn generates ATP. These complexes I, II, III, IV form the respiratory chain.
2- It contains also complex - V (the ATP –synthetase) which carries out ATP – synthesis .
3- The inner membrane folds to form cristae or tubules which
increase the surface area for ATP – synthesis and the respiratory
chain.
4- It contains high concentrations of phospholipid that makes it
nearly impermeable to ions, electrons and protons for isolation of
the matrix from intermembrane space.
ATP –Synthetases (Complex - V): They are Knob-like repeating
units on the inner membrane which project from the inner
membrane toward the matrix. They carry enzyme complex that
store the energy in form of ATP molecules which are synthesized
from ADP and inorganic phosphate.
Mitochondrial Matrix (Intercristal Space)
The matrix of mitochondrion is filled with dense fluid which is formed of fine granular
substance as observed under electron microscope.
1- About 50% of the matrix content is formed of proteins; enzymes that are responsible for:
a) Degradation of fatty acids and pyruvate to acetyl Co–enzyme A.
b) Oxidation of Acetyl Co-enzyme A in Krebs cycle.
c) Synthesis of mitochondrial ribosomes, tRNA and mRNA by DNA transcription.
Circular mitochondrial DNA in matrix and the enzymes are necessary for expression of
mitochondrial genome.
2- Mitochondrial matrix contains also mitochondrial dense granules which are salts of
calcium and magnesium.
2
Mitochondrial abnormalities: Mitochondrial DNA can be abnormal .This interferes with
mitochondrial and cell functions , resulting in disorders referred to as mitochondrial
cytopathy syndromes. The features (which differ in intensity from patient to patient ) include
muscle weakness, degenerative lesions in the brain , and high levels of lactic acid.
Production of ATP by Mitochondria :
Mitochondrion works to produce ATP via aerobic respiration. In aerobic respiration the
following takes place:
1- Mitochondria require oxygen to carry out aerobic respiration, therefore in hypoxia aerobic
respiration and production of ATP stop.
2- During aerobic respiration, the nutrients are catabolized to carbon dioxide and water.
3- Mitochondria store the energy in electrons of hydrogen atoms as phosphate bonds in ATP
molecules.
4- Glucose becomes oxidized; loss of electron, and oxygen becomes reduced, accept the
electrons.
Equation for Aerobic Respiration
By transfer of electron of hydrogen atom (fig. ) in glucose to oxygen, aerobic respiration
uses its energy to synthesize of ATP -molecules. This energy is stored in high energy
phosphate bonds in ATP molecules.
If the energy of glucose is released all at once, it will destroy the cell; therefore the cell
transfers the electron of hydrogen atom in glucose to oxygen in a series of about 30 steps. In
each step it releases apart of energy.
5- The food is the source of high energy electrons that are converted to chemical bonds
carrying stored energy in mitochondria during respiration.
Aerobic Respiration can be divided into 4 successive Stages:1- Glycolysis
3
- It occurs in cytoplasm. It is a cytoplasmic process of anaerobic respiration (process of
respiration in absence of oxygen).
- In which glucose breaks down into pyruvate and 2 ATP -molecules and one molecule of
NADH.
- Anaerobic respiration (glycolysis in cytoplasm) produces 2 ATP -molecules per glucose
molecule.
2- Formation of Acetyl Coenzyme A
Pyruvate enters a mitochondrion and there converts into acetyl CoA + NADH + CO2.
Coenzyme A enters the Krebs’s cycle.
3- Citric acid cycle (Kreb’s cycle)
In addition to all required enzymes, the followings are needed to run the Kreb’s cycle:
a. Pyruvate (electron donors).
b. NAD+ and FAD+ (electron carriers). { NAD = Nicotinamide adenine dinucleotide (Oxidized form
NAD+, reduced form NADH) FAD = Flavin Adenine Dinucleotide (Oxidized form FAD+, reduced form NADH2 }
c. Oxygen (electron acceptors).
Acetyl CoA enters Kreb’s cycle, as the Kreb’s cycle run the electron carriers; NAD+ and
FAD+ accept the electrons of hydrogen and change to the reduced forms NADH and
FADH2. This process also produces 2 ATP-molecules per glucose molecule.
4. Electron Transport and Chemiosmosis
In aerobic respiration process the rest of energy in hydrogen atoms of glucose molecule is
extracted to be used for ATP synthesis.
ADH2 carry the high energy electrons to the electron transport chain and
donate them.
complexes are reduced (accept electrons).
ectrons are passed from one complex to another, some of their energy is used to
move H+ (protons) to the intermembrane space, forming a proton gradient.
space to the matrix takes place through spe-cific
channel in ATP synthetase or complex V located in inner mitochondrial membrane.
results in rotation of the central
part of ATP synthetase in response to the force of protons moving through the enzyme
complex.
redox reactions in
electron transport chain, the entire aerobic respiration process is known as the oxidative
phosphorylation.
The synthesized ATP is released into the cytosol to be used in the different cellular activities.
molecule produces 4 ATP-molecules by substrate
level of phosphorylation, and from 32 to 34 ATP-molecules by oxidative phosphorylation.
Energy from Carbohydrates, Proteins and Fats
4
• Product of the catabolism of carbohydrates, proteins and fats enter glycolysis or citric acid
cycle at various points.
• End products of catabolism are: NH3, H2O and CO2.
Fig.: Diagram illustrates the process of aerobic respiration. It includes formation of acetyl CoA which enters Kreb’s cycle in
the matrix, transport of electrons to electron transport chain in inner membrane by NADH & FADH2 and synthesis of ATP by
complex -V, and reduction of O2 into H2O.
5