RT Journal Article
SR Electronic
T1 ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202000918
DO 10.26508/lsa.202000918
VO 4
IS 3
A1 Tianyao Xiao
A1 Viplendra PS Shakya
A1 Adam L Hughes
YR 2021
UL https://www.life-science-alliance.org/content/4/3/e202000918.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 in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting to other organelles. Amongst organelles, the ER has emerged as a key destination for a subset of non-imported mitochondrial proteins. However, how ER targeting of various types of mitochondrial proteins is achieved remains incompletely understood. Here, we show that the ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway. Overall, this study outlines an important role for the GET complex in ER targeting of non-imported mitochondrial carrier proteins.