Mitochondrial Protein Synthesis Adapts to Influx of Nuclear-Encoded Protein.
Mitochondrial ribosomes translate membrane integral core subunits of the oxidative phosphorylation system encoded by mtDNA. These translation products associate with nuclear-encoded, imported proteins to form enzyme complexes that produce ATP. Here, we show that human mitochondrial ribosomes display translational plasticity to cope with the supply of imported nuclear-encoded subunits. Ribosomes expressing mitochondrial-encoded COX1 mRNA selectively engage with cytochrome c oxidase assembly factors in the inner membrane. Assembly defects of the cytochrome c oxidase arrest mitochondrial translation in a ribosome nascent chain complex with a partially membrane-inserted COX1 translation product. This complex represents a primed state of the translation product that can be retrieved for assembly. These findings establish a mammalian translational plasticity pathway in mitochondria that enables adaptation of mitochondrial protein synthesis to the influx of nuclear-encoded subunits.
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Ricarda
R
Richter-Dennerlein
Department of Biochemistry and Functional Proteomics, Faculty of Biology, University Freiburg, 79104 Freiburg, Germany.
Silke
S
Oeljeklaus
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Isotta
I
Lorenzi
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Christin
C
Ronsör
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Bettina
B
Bareth
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Alexander Benjamin
AB
Schendzielorz
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Cong
C
Wang
Department of Biochemistry and Functional Proteomics, Faculty of Biology, University Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
Bettina
B
Warscheid
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany; Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. Electronic address: peter.rehling@medizin.uni-goettingen.de.
Peter
P
Rehling
Department of Cellular Biochemistry, University Medical Centre Göttingen, GZMB, 37073 Göttingen, Germany.
Sven
S
Dennerlein
D021581:Active Transport, Cell Nucleus; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000235:genetics; D003576:Electron Transport Complex IV / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D000077278:RNA, Mitochondrial; D012270:Ribosomes / Q000378:metabolism
C578539:COA3 protein, human; C570605:COX14 protein, human; D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; C029305:mitochondrial messenger RNA; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D003576:Electron Transport Complex IV
C12ORF62; COX1; MITRAC; OXPHOS; assembly; cytochrome c oxidase; mitochondrial ribosome; mitochondrial translation; translation regulation; translational plasticity
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