Journal Article

DZNE-2020-03332

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.

Rolland, S. G. (Corresponding author) ; Motori, E. ; Memar, N. ; Hench, J. ; Frank, S. ; Winklhofer, K. F.DZNE* ; Conradt, B.

2013
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1303872110

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.

Keyword(s): Adenosine Triphosphate: metabolism (MeSH) ; Animals (MeSH) ; Animals, Genetically Modified (MeSH) ; Blotting, Western (MeSH) ; Caenorhabditis elegans: genetics (MeSH) ; Caenorhabditis elegans: metabolism (MeSH) ; Caenorhabditis elegans Proteins: genetics (MeSH) ; Caenorhabditis elegans Proteins: metabolism (MeSH) ; Cell Line (MeSH) ; Cell Line, Tumor (MeSH) ; DNA-Binding Proteins: genetics (MeSH) ; DNA-Binding Proteins: metabolism (MeSH) ; Electron Transport Complex IV: metabolism (MeSH) ; GTP Phosphohydrolases: genetics (MeSH) ; GTP Phosphohydrolases: metabolism (MeSH) ; Green Fluorescent Proteins: genetics (MeSH) ; Green Fluorescent Proteins: metabolism (MeSH) ; Humans (MeSH) ; Leigh Disease: genetics (MeSH) ; Leigh Disease: metabolism (MeSH) ; Leigh Disease: pathology (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Microscopy, Fluorescence (MeSH) ; Mitochondria: genetics (MeSH) ; Mitochondria: metabolism (MeSH) ; Mitochondrial Proteins: genetics (MeSH) ; Mitochondrial Proteins: metabolism (MeSH) ; Neoplasm Proteins: genetics (MeSH) ; Neoplasm Proteins: metabolism (MeSH) ; RNA Interference (MeSH) ; Transcription Factors: genetics (MeSH) ; Transcription Factors: metabolism (MeSH) ; Caenorhabditis elegans Proteins ; DNA-Binding Proteins ; LRPPRC protein, human ; MMA-1 protein, C elegans ; Membrane Proteins ; Mitochondrial Proteins ; Neoplasm Proteins ; SCO1 protein, human ; TFAM protein, human ; Transcription Factors ; Green Fluorescent Proteins ; Adenosine Triphosphate ; Electron Transport Complex IV ; GTP Phosphohydrolases ; OPA1 protein, human

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Contributing Institute(s):

1. Neurobiochemistry (AG Winklhofer)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2013

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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