Back to Search
Start Over
Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis
- Source :
- Cell metabolism. 27(6)
- Publication Year :
- 2017
-
Abstract
- Cellular proteostasis is maintained via the coordinated synthesis, maintenance, and breakdown of proteins in the cytosol and organelles. While biogenesis of the mitochondrial membrane complexes that execute oxidative phosphorylation depends on cytoplasmic translation, it is unknown how translation within mitochondria impacts cytoplasmic proteostasis and nuclear gene expression. Here we have analyzed the effects of mutations in the highly conserved accuracy center of the yeast mitoribosome. Decreased accuracy of mitochondrial translation shortened chronological lifespan, impaired management of cytosolic protein aggregates, and elicited a general transcriptional stress response. In striking contrast, increased accuracy extended lifespan, improved cytosolic aggregate clearance, and suppressed a normally stress-induced, Msn2/4-dependent interorganellar proteostasis transcription program (IPTP) that regulates genes important for mitochondrial proteostasis. Collectively, the data demonstrate that cytosolic protein homeostasis and nuclear stress signaling are controlled by mitochondrial translation efficiency in an inter-connected organelle quality control network that determines cellular lifespan.
- Subjects :
- 0301 basic medicine
Saccharomyces cerevisiae Proteins
Physiology
Mitochondrial translation
Saccharomyces cerevisiae
Protein aggregation
Mitochondrion
Biology
Mitochondrial Proteins
Mitochondrial Ribosomes
03 medical and health sciences
Phosphatidylinositol 3-Kinases
0302 clinical medicine
Mitochondrial ribosome
Inner mitochondrial membrane
Molecular Biology
Cell Nucleus
Cytoplasmic translation
Cell Biology
Cell biology
Mitochondria
DNA-Binding Proteins
Cytosol
030104 developmental biology
Proteostasis
Gene Expression Regulation
Protein Biosynthesis
Reactive Oxygen Species
030217 neurology & neurosurgery
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 19327420
- Volume :
- 27
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Cell metabolism
- Accession number :
- edsair.doi.dedup.....55340001a70f26a70db87b5c265f7ab6