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Cellular respiration is the process of oxidizing food molecules, like glucose, to carbon dioxide and water.
C6H12O6 + 6O2 + 6H2O → 12H2O + 6 CO2
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:Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Their number within the cell ranges from a few hundred to, in very active cells, thousands. Their main function is the conversion of the potential energy of food molecules into ATP.
Mitochondria have:
This electron micrograph (courtesy of Keith R. Porter) shows a single mitochondrion from a bat pancreas cell. Note the double membrane and the way the inner membrane is folded into cristae. The dark, membrane-bound objects above the mitochondrion are lysosomes.
The number of mitochondria in a cell can
(Defects in either process can produce serious, even fatal, illness.)
The matrix contains a complex mixture of soluble enzymes that catalyze the respiration of pyruvic acid and other small organic molecules.
Here pyruvic acid is
The citric acid cycle is also known as the Krebs cycle (after the biochemist who worked it out) and the tricarboxylic acid cycle (TCA). The steps:
The electrons of NADH and FADH2 are transferred to the electron transport chain.
The electron transport chain consists of 3 complexes of integral membrane proteins
The electron transport chain accomplishes:
(Electrons from FADH2 enter the electron transport chain through another integral membrane protein — complex II — reducing ubiquinone (see figure on right).
(Cytochrome c can only transfer one electron at a time, so cytochrome c oxidase must wait until it has accumulated 4 of them before it can react with oxygen.)
The energy released as electrons pass down the gradient from NADH to oxygen is harnessed by three enzyme complexes of the respiratory chain (I, III, and IV) to pump protons (H+) against their concentration gradient from the matrix of the mitochondrion into the intermembrane space (an example of active transport).
As their concentration increases there (which is the same as saying that the pH decreases), a strong diffusion gradient is set up. The only exit for these protons is through the ATP synthase complex. As in chloroplasts, the energy released as these protons flow down their gradient is harnessed to the synthesis of ATP. The process is called chemiosmosis and is an example of facilitated diffusion.
One-half of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their discovery of how ATP synthase works. Link to some of the details.
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It is tempting to try to view the synthesis of ATP as a simple matter of stoichiometry (the fixed ratios of reactants to products in a chemical reaction). But (with 3 exceptions) it is not.
Most of the ATP is generated by the proton gradient that develops across the inner mitochondrial membrane. The number of protons pumped out as electrons drop from NADH through the respiratory chain to oxygen is theoretically large enough to generate, as they return through ATP synthase, 3 ATPs per electron pair (but only 2 ATPs for each pair donated by FADH2).
With 12 pairs of electrons removed from each glucose molecule,
Add to this the 4 ATPs that are generated by the 3 exceptions and one arrives at 38.
But
So the actual yield of ATP as mitochondria respire varies with conditions. It probably seldom exceeds 30.
The human mitochondrion contains 5–10 identical, circular molecules of DNA. Each consists of 16,569 base pairs carrying the information for 37 genes which encode:
The rRNA and tRNA molecules are used in the machinery that synthesizes the 13 proteins.
The 13 proteins participate in building several protein complexes embedded in the inner mitochondrial membrane.Each of these protein complexes also requires subunits that are encoded by nuclear genes, synthesized in the cytosol, and imported from the cytosol into the mitochondrion. Nuclear genes also encode ~1,000 other proteins that must be imported into the mitochondrion. [More]
Although many different organs may be affected, disorders of the muscles and brain are the most common. Perhaps this reflects the great demand for energy of both these organs. (Although representing only ~2% of our body weight, the brain consumes ~20% of the energy produced when we are at rest.)
Some of these disorders are inherited in the germline. In the vast majority of cases, the mutant gene is received from the mother because only very rarely do the mitochondria in sperm survive in the fertilized egg.
Other disorders are somatic; that is, the mutation occurs in the somatic tissues of the individual. These disorders can be caused not only by mutations in mtDNA, but also by mutations in the 228 nuclear genes that have also been implicated in human mitochondrial diseases. These latter mutations can be inherited from the father as well as the mother.
A number of humans who suffer from easily-fatigued muscles turn out to have a mutations in their cytochrome b gene. Curiously, only the mitochondria in their muscles have the mutation; the mtDNA of their other tissues is normal. Presumably, very early in their embryonic development, a mutation occurred in a cytochrome b gene in the mitochondrion of a cell destined to produce their muscles.
The severity of mitochondrial diseases varies greatly. The reason for this is probably the extensive mixing of mutant DNA and normal DNA in the mitochondria as they fuse with one another. A mixture of both is called heteroplasmy. The higher the ratio of mutant to normal, the greater the severity of the disease. In fact by chance alone, cells can on occasion end up with all their mitochondria carrying all-mutant genomes — a condition called homoplasmy (a phenomenon resembling genetic drift).
Mutations in some 228 nuclear genes have also been implicated in human mitochondrial diseases, but mitochondrial replacement techniques will not be able to help with these.
Many of the features of the mitochondrial genetic system resemble those found in bacteria. This has strengthened the theory that mitochondria are the evolutionary descendants of a bacterium that established an endosymbiotic relationship with the ancestors of eukaryotic cells early in the history of life on earth. However, many of the genes needed for mitochondrial function have since moved to the nuclear genome.
The recent sequencing of the complete genome of the endosymbiotic alpha-proteobacterium Rickettsia prowazekii has revealed a number of genes closely related to those found in mitochondria. This suggests a shared ancestry.
| Further discussion of the evolutionary implications of mtDNA. |
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