Much of our current knowledge about mitochondria has come from studying patients who have respiratory chain disorders. These disorders comprise a large collection of individually rare syndromes, each presenting in a unique and often devastating way. In recent years, there has been great progress in defining their genetic basis, but we still know little about the cascade of events that gives rise to such diverse pathology. Here, we review these disorders and explore them in the context of a contemporary understanding of mitochondrial evolution, biochemistry and genetics. Fully deciphering their pathogenesis is a challenging next step that will inspire the development of drug treatments for rare and common diseases.
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We apologize to the many authors whose work we were unable to cite because of space limitations. We offer special thanks to D. Thorburn for careful review of the manuscript and his help with compiling an updated list of disease genes. We are grateful to S. Calvo, M. Jain, E. Rosen, V. Siegel and M. Gray for thoughtful feedback on the manuscript; J-.P. Mazat for providing a figure; M. Fleming, A. Sadun, M. Seidman, R. Mitchell, R. Saneto, D. McGuone and L. Rodriguez for providing clinical images; and G. Perkins and M. Ellisman for providing electron micrographs. We thank the National Institutes of Health for ongoing grant support.
The authors declare no competing financial interests.
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Vafai, S., Mootha, V. Mitochondrial disorders as windows into an ancient organelle. Nature 491, 374–383 (2012). https://doi.org/10.1038/nature11707
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