Joanna Poulton, University of Oxford, Oxford, UK
Laurence Bindoff, Haukeland Hospital, Haukeland Hospital, Bergen, Norway
Published online: April 2001
DOI: 10.1038/npg.els.0002287
Mitochondrial diseases are rare multisystem diseases primarily affecting muscle, brain, heart and liver. The unique biology of the mitochondrion causes variability in phenotypic severity and transmission.
Keywords: mitochondrial DNA; MELAS; MERRF; NARP; LHON
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Figure 1.
The mitochondrial respiratory chain (MRC). Reduced cofactors such as NADH and flavoproteins (as found in succinate dehydrogenase) are reoxidized by the MRC. In the process, electrons are donated into the MRC and subsequently pass from complex to complex down an energy gradient. Sufficient energy is generated at three steps (complexes I, III and IV) to drive the extrusion of protons (H+) that cannot re‐enter the inner membrane. This creates an electrochemical gradient, which is discharged back into the mitochondrion via complex V; the energy this generates is used to drive phosphorylation of ADP to ATP. Thus, substrate oxidation is linked to phosphorylation of ADP; hence, oxidative phosphorylation. The final electron acceptor is molecular oxygen. |
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Figure 2.
The normal mitochondrial genome. Coding information is contained on both strands, in nonoverlapping units. The strands can be separated by density centrifugation into heavy (H strand) and light (L strand). An approximately 1‐kb region, called the D‐loop, contains the control elements, including transcription start sites for both H and L strands and replication start site for the H strand. Only 13 proteins of the 70 or more proteins in the mitochondrial respiratory chain are encoded by mtDNA. The vast majority, therefore, are synthesized in the cytoplasm and imported into the mitochondrion. Circles represent genes for transfer RNAs (tRNAs). Note that there are two tRNA genes for leucine (a) and two for serine (b) otherwise there are only single tRNA genes for each amino acid. OH; origin of replication of the heavy strand; OL, origin of replication of the light strand. ATPase 6 and 8 (lilac), subunits 6 and 8 of ATP synthetase; COX genes (blue), subunits I to III of cytochrome c oxidase; cyt b (orange), cytochrome b; ND genes (red), subunits 1–6 and 4L of NADH dehydrogenase. |
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Further Reading
Attardi G and Schatz G (1988) Biogenesis of mitochondria. Annual Review of Cell Biology 4: 289–333.
Bindoff LA, Brown G and Poulton J (1997) Mitochondrial myopathies. In: Emery AEH (ed.) Diagnostic Criteria for Neuromuscular Disorders, pp. 85–90. London: RSM Press
Darley‐Usmar V and Schapira AHV (1994) Mitochondria: DNA, Proteins and Disease. London: Portland Press.
Enriquez JA and Attardi G (1996) Evidence for aminoacylation‐induced conformational changes in human mitochondrial tRNAs. Proceedings of the National Academy of Sciences of the USA 93: 8300–8305.
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Shoffner JM, Lott MT, Lezza AM et al. (1990) Myoclonic epilepsy and ragged‐red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell 61: 931–937.
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Tiranti V, Jaksch M, Hofmann S et al. (1999) Loss‐of‐function mutations of SURF‐1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency. Annals of Neurology 46: 161–166.
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