Quality control of mitochondrial protein synthesis is required for membrane integrity and cell fitness.
Mitochondrial ribosomes synthesize a subset of hydrophobic proteins required for assembly of the oxidative phosphorylation complexes. This process requires temporal and spatial coordination and regulation, so quality control of mitochondrial protein synthesis is paramount to maintain proteostasis. We show how impaired turnover of de novo mitochondrial proteins leads to aberrant protein accumulation in the mitochondrial inner membrane. This creates a stress in the inner membrane that progressively dissipates the mitochondrial membrane potential, which in turn stalls mitochondrial protein synthesis and fragments the mitochondrial network. The mitochondrial m-AAA protease subunit AFG3L2 is critical to this surveillance mechanism that we propose acts as a sensor to couple the synthesis of mitochondrial proteins with organelle fitness, thus ensuring coordinated assembly of the oxidative phosphorylation complexes from two sets of ribosomes.
Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Uwe
U
Richter
Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Taina
T
Lahtinen
Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Paula
P
Marttinen
Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
Fumi
F
Suomi
Research Programs for Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland brendan.battersby@helsinki.fi.
Brendan J
BJ
Battersby
D049069:ATP-Dependent Proteases / Q000235:genetics / Q000378:metabolism*; D000074183:ATPases Associated with Diverse Cellular Activities; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D010085:Oxidative Phosphorylation; D010086:Oxidative Phosphorylation Coupling Factors / Q000096:biosynthesis; D014176:Protein Biosynthesis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering
D006877:Hydroxamic Acids; D024101:Mitochondrial Proteins; D010086:Oxidative Phosphorylation Coupling Factors; D034741:RNA, Small Interfering; D045726:Metalloproteases; C572960:OMA1 protein, mouse; D049069:ATP-Dependent Proteases; C542395:Afg3l2 protein, mouse; D000581:Amidohydrolases; C084507:peptide deformylase; C530489:ATP5b protein, mouse; D025261:Mitochondrial Proton-Translocating ATPases; D000074183:ATPases Associated with Diverse Cellular Activities; C010531:actinonin