RT Journal Article
SR Electronic
T1 The GET pathway safeguards against non-imported mitochondrial protein stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.26.173831
DO 10.1101/2020.06.26.173831
A1 Tianyao Xiao
A1 Viplendra P.S. Shakya
A1 Adam L. Hughes
YR 2020
UL http://biorxiv.org/content/early/2020/06/26/2020.06.26.173831.abstract
AB Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified, including proteasomal destruction, deposition into protein aggregates, and mis-targeting to other organelles. Amongst organelles, the endoplasmic reticulum (ER) has emerged as a key destination for non-imported mitochondrial proteins, but how ER-targeting of these proteins is achieved remains unclear. Here, we show that the guided entry of tail-anchored proteins (GET) complex is required for ER-targeting of endogenous mitochondrial multi-transmembrane proteins. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. The ER targeting of non-imported mitochondrial proteins by the GET complex prevents cellular toxicity and facilitates re-import of mitochondrial proteins from the ER via the recently identified ER-SURF pathway. Overall, this study outlines an important and unconventional role for the GET complex in mitigating stress associated with non-imported mitochondrial proteins.Competing Interest StatementThe authors have declared no competing interest.