Mitochondrial protein translocation-associated degradation
Mårtensson CU, Priesnitz C, Song J, Ellenrieder L, Doan KN, Boos F, Floerchinger A, Zufall N, Oeljeklaus S, Warscheid B, Becker T.
Mitochondrial functions and biogeneses depend on the uptake of about 1000 proteins that are produced as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) transports most of these preproteins into mitochondria. Defects in protein import leads to a number of cellular stress response. However, a constitutive surveillance system that ensure protein import via the TOM channel under non-stress conditions was not identified yet. We report here that in Saccharomyces cerevisiae a fraction of Ubx2 that also functions in endoplasmic reticulum-associated degradation plays a central in quality control of mitochondrial protein import. A fraction of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the translocation channel. This mitochondrial translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex to prevent clogging of the translocation pore. Thus, the mitoTAD pathways protects the cell against proteotoxic stress induced by impaired protein import into mitochondria.
