An ER surface retrieval pathway safeguards the import of mitochondrial membrane proteins in yeast

The majority of organellar proteins are translated on cytosolic ribosomes and must be sorted correctly to function.Targeting routes have been identified for organelles such as peroxisomes and the endoplasmic reticulum (ER). However, little is known about the initial steps of targeting of mitochondrial proteins. In this study, we used a genome-wide screen in yeast and identified factors critical for the intracellular sorting of themitochondrial innermembrane protein Oxa1.The screen uncovered an unexpected path, termed ER-SURF, for targeting ofmitochondrialmembrane proteins.This pathway retrieves mitochondrial proteins from the ER surface and reroutes them to mitochondria with the aid of the ER-localized chaperone Djp1. Hence, cells use the expanse of the ERsurfaces as a fail-safe tomaximize productive mitochondrial protein targeting.