Journal Article

Mitochondrial protein translocation-associated degradation

Oeljeklaus, Silke, Doan, Kim Nguyen, Warscheid, Bettina, Priesnitz, Chantal, Zufall, Nicole, Ellenrieder, Lars, Becker, Thomas, Floerchinger, Alessia, Mårtensson, Christoph U., Song, Jiyao, Boos, Felix

2019

Overview

Mitochondrial biogenesis and functions depend on the import of precursor proteins via the ‘translocase of the outer membrane’ (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria. In Saccharomyces cerevisiae , Ubx2 promotes clearing trapped precursor proteins from the channel of the translocase of the outer membrane, in a translocation-associated degradation pathway that maintains the protein import capacity of mitochondria.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 14/35 / 38/77 / 42/70 / 631/45/474/1768 / 631/45/612/1240 / 631/80/2023/2022 / 631/80/642/333 / 82/16 / 82/29 / 82/83 / 96/34 / Analysis / Biodegradation / Carrier Proteins - metabolism / Endoplasmic Reticulum-Associated Degradation / Humanities and Social Sciences / Membrane proteins / Membrane Proteins - metabolism / Methods / Mitochondria - metabolism / Mitochondrial biogenesis / Mitochondrial Membrane Transport Proteins - metabolism / Mitochondrial Precursor Protein Import Complex Proteins / Mitochondrial Proteins - metabolism / multidisciplinary / Protein Transport / Proteolysis / Saccharomyces cerevisiae - cytology / Saccharomyces cerevisiae - metabolism / Saccharomyces cerevisiae Proteins - metabolism / Science / Science (multidisciplinary) / Translocations (Genetics) / Valosin Containing Protein - metabolism