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Abstract
Mitochondria contain their own genetic material and evolved from prokaryotic ancestors some two billion years ago. They are the main source of the cell’s energy supply and are involved in such important processes as apoptosis, mitochondrial diseases and aging. Mitochondria display a complex dynamical behavior involving cycles of fusion and fission, the function of which is as yet unknown. We recently proposed a concise theory that explains: (i) why fusion and fission have evolved, (ii) how these processes relate to the accumulation of mitochondrial mutants during aging, and (iii) why mtDNA is located close to the respiration complexes where most radicals are generated. We also believe that this ‘organelle control’ theory may explain why mutations in mitochondrial tRNA genes are the most prevalent kind of defect associated with inherited human mitochondrial diseases, despite the fact that mt-tRNA genes account for only 5% of the mtDNA coding sequence.
Acknowledgments
T.B.L.K. is supported by the BBSRC Centre for Integrated Systems Biology of Aging and Nutrition and by the UK NIHR Biomedical Research Centre for Aging and Age-related disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust. A.K. was supported by a grant of the BMBF (‘GerontoMitoSys’). Furthermore, this work was partly funded by a Glenn Foundation award to T.B.L.K.
Figures and Tables
Figure 1 Key ingredients of the organelle control theory. Most mitochondrial proteins are encoded in the nucleus and an optimal supply of the different mitochondria can only be achieved if fusion equilibrates all protein concentrations. But since this also allows the accumulation of mtDNA mutants, fission and selective degradation of defective fragments is necessary. See text for details.
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