REVIEW: Does Mitochondrial Fusion Require Transmembrane Potential?

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I. E. Karavaeva¹, K. V. Shekhireva¹, F. F. Severin², and D. A. Knorre^2*

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; E-mail: knorre@belozersky.msu.ru

^* To whom correspondence should be addressed.

Received December 23, 2014; Revision received January 13, 2015

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Dissipation of transmembrane potential inhibits mitochondrial fusion and thus prevents reintegration of damaged mitochondria into the mitochondrial network. Consequently, damaged mitochondria are removed by autophagy. Does transmembrane potential directly regulate the mitochondrial fusion machinery? It was shown that inhibition of ATP-synthase induces fragmentation of mitochondria while preserving transmembrane potential. Moreover, mitochondria of the yeast Saccharomyces cerevisiae retain the ability to fuse even in the absence of transmembrane potential. Metazoan mitochondria in some cases retain ability to fuse for a short period even in a depolarized state. It also seems unlikely that transmembrane potential-based regulation of mitochondrial fusion would prevent reintegration of mitochondria with damaged ATP-synthase into the mitochondrial network. Such reintegration could lead to clonal expansion of mtDNAs harboring deleterious mutations in ATP synthase. We speculate that transmembrane potential is not directly involved in regulation of mitochondrial fusion but affects mitochondrial NTP/NDP ratio, which in turn regulates their fusion.

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KEY WORDS: mitochondria, fusion, fission, membrane potential, mtDNA, regulation

DOI: 10.1134/S0006297915050053

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