Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis

作者：Suhm Tamara; Kaimal Jayasankar Mohanakrishnan; Dawitz Hannah; Peselj Carlotta; Masser Anna E; Hanzen Sarah; Ambrozic Matevz; Smialowska Agata; Bjorck Markus L; Brzezinski Peter; Nystrom Thomas; Buttner Sabrina; Andreasson Claes^*; Ott Martin^*

来源：Cell Metabolism, 2018, 27(6): 1309-+.

DOI：10.1016/j.cmet.2018.04.011

Cellular proteostasis ismaintained 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 interor-ganellar 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.

• 出版日期2018-6-5