TY  - JOUR
AU  - Rolland, Stéphane G
AU  - Motori, Elisa
AU  - Memar, Nadin
AU  - Hench, Jürgen
AU  - Frank, Stephan
AU  - Winklhofer, Konstanze F
AU  - Conradt, Barbara
TI  - Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 110
IS  - 32
SN  - 0027-8424
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DZNE-2020-03332
SP  - E2967-E2976
PY  - 2013
AB  - 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.
KW  - Adenosine Triphosphate: metabolism
KW  - Animals
KW  - Animals, Genetically Modified
KW  - Blotting, Western
KW  - Caenorhabditis elegans: genetics
KW  - Caenorhabditis elegans: metabolism
KW  - Caenorhabditis elegans Proteins: genetics
KW  - Caenorhabditis elegans Proteins: metabolism
KW  - Cell Line
KW  - Cell Line, Tumor
KW  - DNA-Binding Proteins: genetics
KW  - DNA-Binding Proteins: metabolism
KW  - Electron Transport Complex IV: metabolism
KW  - GTP Phosphohydrolases: genetics
KW  - GTP Phosphohydrolases: metabolism
KW  - Green Fluorescent Proteins: genetics
KW  - Green Fluorescent Proteins: metabolism
KW  - Humans
KW  - Leigh Disease: genetics
KW  - Leigh Disease: metabolism
KW  - Leigh Disease: pathology
KW  - Membrane Proteins: genetics
KW  - Membrane Proteins: metabolism
KW  - Microscopy, Fluorescence
KW  - Mitochondria: genetics
KW  - Mitochondria: metabolism
KW  - Mitochondrial Proteins: genetics
KW  - Mitochondrial Proteins: metabolism
KW  - Neoplasm Proteins: genetics
KW  - Neoplasm Proteins: metabolism
KW  - RNA Interference
KW  - Transcription Factors: genetics
KW  - Transcription Factors: metabolism
KW  - Caenorhabditis elegans Proteins (NLM Chemicals)
KW  - DNA-Binding Proteins (NLM Chemicals)
KW  - LRPPRC protein, human (NLM Chemicals)
KW  - MMA-1 protein, C elegans (NLM Chemicals)
KW  - Membrane Proteins (NLM Chemicals)
KW  - Mitochondrial Proteins (NLM Chemicals)
KW  - Neoplasm Proteins (NLM Chemicals)
KW  - SCO1 protein, human (NLM Chemicals)
KW  - TFAM protein, human (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
KW  - Green Fluorescent Proteins (NLM Chemicals)
KW  - Adenosine Triphosphate (NLM Chemicals)
KW  - Electron Transport Complex IV (NLM Chemicals)
KW  - GTP Phosphohydrolases (NLM Chemicals)
KW  - OPA1 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:23878239
C2  - pmc:PMC3740885
DO  - DOI:10.1073/pnas.1303872110
UR  - https://pub.dzne.de/record/137010
ER  -