Thursday, 25 September 2014

Global Genetic Determinants of Mitochondrial DNA Copy Number

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0105242

These guys screen yeast for nuclear genes whose deletions lead to a disappearance of mtDNA. Lots of the hits are mitochondrial proteins (54.9%), including a really big set involved in the mitochondrial ribosome. Other hits include a dozen genes involved in nucleic acid metabolism, ATP(4, 5, 14) and GRX (involved in Fe-S cluster formation) and a couple of dozen of miscellaneous functionality. Interesting to speculate on the mechanisms leading to mtDNA loss -- autophagy due to mitochondrial dysfunction, or some more direct mechanism? If the autophagy link is the case, and mitochondrial dysfunction is recognised through membrane potential, then the ATP genes are interesting, as the mitochondrion can presumably (?) maintain its membrane potential without Complex V. Perhaps there's a role for ROS signalling marking a dysfunctional mitochondrion here? If the absence of Complex V means the other complexes end up pumping protons against a higher and higher gradient, churning out more ROS as they do so?

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