PT  - JOURNAL ARTICLE
AU  - Tianyao Xiao
AU  - Viplendra PS Shakya
AU  - Adam L Hughes
TI  - ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway
AID  - 10.26508/lsa.202000918
DP  - 2021 Mar 01
TA  - Life Science Alliance
PG  - e202000918
VI  - 4
IP  - 3
4099  - https://www.life-science-alliance.org/content/4/3/e202000918.short
4100  - https://www.life-science-alliance.org/content/4/3/e202000918.full
SO  - Life Sci. Alliance2021 Mar 01; 4
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.