title: Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.
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.
authors.affiliation: Department Biology II, Center for Integrated Protein Science, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany. rolland@bio.lmu.de
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Rolland
authors.forename: Elisa
authors.initials: E
authors.lastname: Motori
authors.forename: Nadin
authors.initials: N
authors.lastname: Memar
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hench
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
authors.forename: Konstanze F
authors.initials: KF
authors.lastname: Winklhofer
authors.forename: Barbara
authors.initials: B
authors.lastname: Conradt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007888:Leigh Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C087940:LRPPRC protein, human; C584057:MMA-1 protein, C elegans; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C489345:SCO1 protein, human; C499631:TFAM protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: cytochrome c oxidase deficiency neurodegeneration; mitochondrial dynamics