Clearing tail-anchored proteins from mitochondria.

Abstract

Eukaryotic cells contain numerous membrane-bound compartments—the cell organelles. The vast majority of organellar proteins are synthesized as precursors on cytosolic ribosomes and have to be transported to their intracellular destinations (1). The precursor proteins contain organelle-specific targeting signals. Protein machineries located in the cytosol and organelles recognize the precursor proteins and promote their translocation into the organelles. Errors in protein targeting will lead to a mislocalization of proteins with detrimental effects to cell organelles. Thus, in addition to the targeting machineries, quality control systems are important to prevent mistargeting or remove mislocalized proteins from the wrong organelle (2). In PNAS, Okreglak and Walter (3) report the identification of a quality control system of the mitochondrial outer membrane. Using budding yeast as a model system, they show that a membrane-bound ATPase is a crucial player in a surveillance pathway that detects and extracts mistargeted tail-anchored membrane proteins.