%0 Journal Article
%A Rolland, Stéphane G
%A Motori, Elisa
%A Memar, Nadin
%A Hench, Jürgen
%A Frank, Stephan
%A Winklhofer, Konstanze F
%A Conradt, Barbara
%T Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.
%J Proceedings of the National Academy of Sciences of the United States of America
%V 110
%N 32
%@ 0027-8424
%C Washington, DC
%I National Acad. of Sciences
%M DZNE-2020-03332
%P E2967-E2976
%D 2013
%X 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.
%K Adenosine Triphosphate: metabolism
%K Animals
%K Animals, Genetically Modified
%K Blotting, Western
%K Caenorhabditis elegans: genetics
%K Caenorhabditis elegans: metabolism
%K Caenorhabditis elegans Proteins: genetics
%K Caenorhabditis elegans Proteins: metabolism
%K Cell Line
%K Cell Line, Tumor
%K DNA-Binding Proteins: genetics
%K DNA-Binding Proteins: metabolism
%K Electron Transport Complex IV: metabolism
%K GTP Phosphohydrolases: genetics
%K GTP Phosphohydrolases: metabolism
%K Green Fluorescent Proteins: genetics
%K Green Fluorescent Proteins: metabolism
%K Humans
%K Leigh Disease: genetics
%K Leigh Disease: metabolism
%K Leigh Disease: pathology
%K Membrane Proteins: genetics
%K Membrane Proteins: metabolism
%K Microscopy, Fluorescence
%K Mitochondria: genetics
%K Mitochondria: metabolism
%K Mitochondrial Proteins: genetics
%K Mitochondrial Proteins: metabolism
%K Neoplasm Proteins: genetics
%K Neoplasm Proteins: metabolism
%K RNA Interference
%K Transcription Factors: genetics
%K Transcription Factors: metabolism
%K Caenorhabditis elegans Proteins (NLM Chemicals)
%K DNA-Binding Proteins (NLM Chemicals)
%K LRPPRC protein, human (NLM Chemicals)
%K MMA-1 protein, C elegans (NLM Chemicals)
%K Membrane Proteins (NLM Chemicals)
%K Mitochondrial Proteins (NLM Chemicals)
%K Neoplasm Proteins (NLM Chemicals)
%K SCO1 protein, human (NLM Chemicals)
%K TFAM protein, human (NLM Chemicals)
%K Transcription Factors (NLM Chemicals)
%K Green Fluorescent Proteins (NLM Chemicals)
%K Adenosine Triphosphate (NLM Chemicals)
%K Electron Transport Complex IV (NLM Chemicals)
%K GTP Phosphohydrolases (NLM Chemicals)
%K OPA1 protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23878239
%2 pmc:PMC3740885
%R 10.1073/pnas.1303872110
%U https://pub.dzne.de/record/137010