Mitochondria -Mitochondria are the “power-house” of the cells. -They perform oxidative phosphorylation for production of energy and able to synthesize lipid, certain amino acid and heme group. Mitochondria are able to multiply; they possess their own DNA for self-replication . -It have dramatic changes in shpe by fusion and fission.

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 .

cristae-type mitochondria

tubular mitochondria

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. 10-Parkinson’s disease (PD) 11-Human aging.

Structure of mitochondria 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

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.

1- It contains complexes - I, II, III, IV, V 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.

Electron Transport Respiratory Chain

Mitochondrial Matrix (Inter-cristal 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.

Mitochondrial abnormalities 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

Aerobic Respiration can be divided into 4 successive Stages:- 1- Glycolysis It is a cytoplasmic process of anaerobic respiration In which glucose breaks down into pyruvate and 2 ATP -molecules and one molecule of NADH. 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).

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. - NADH and FADH2 carry the high energy electrons to the electron transport chain and donate them.

Types of electron carrier 1-Flavoprotein 2-cytochromes 3-Three copper atoms 4-Ubiquinone 5-Iron-sulfer protein

Energy from Carbohydrates, Proteins and Fats Product of the catabolism of carbohydrates, proteins and fats enter glycolysis or citric acid cycle at various points. The process of oxidative phosphorylation can product of more than 2 x 1026 molecules of ATP in our bodies per day. • End products of catabolism are: NH3, H2O and CO2.

Q1- Are Mitochondrial disorders inherited by maternal or paternal? Why? Q2-Why cause mutations in mtDNA than nuclear DNA? Q3-Which type of cells have mutant mitochondria? Q4-what is the Parkinsons disease (PD) Q5-Are mutation in mtDNA caused human aging? Who?

Questions about peroxisomes Q1-What is Zellweger syndrome? Q2-What is (Lorenzos oil) adrenoleukodystrophy (ALD)?

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