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Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E2967-76. doi: 10.1073/pnas.1303872110. Epub 2013 Jul 22.

Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.

Author information

1
Department Biology II, Center for Integrated Protein Science, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany. rolland@bio.lmu.de

Abstract

Mitochondrial morphology changes in response to various stimuli but the significance of this is unclear. In a screen for mutants with abnormal mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function also decreases the activity of complex IV of the electron transport chain, however without affecting cellular ATP levels. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to mitochondrial fragmentation and decreased levels of ATP. These findings indicate that in a mma-1/LRPPRC-deficient background, hyperfusion allows mitochondria to maintain their functions despite a reduction in complex IV activity. Our data reveal an evolutionary conserved mechanism that is triggered by reduced complex IV function and that induces mitochondrial hyperfusion to transiently compensate for a drop in the activity of the electron transport chain.

KEYWORDS:

cytochrome c oxidase deficiency neurodegeneration; mitochondrial dynamics

PMID:
23878239
PMCID:
PMC3740885
DOI:
10.1073/pnas.1303872110
[Indexed for MEDLINE]
Free PMC Article

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