RNA promotes mitochondrial import of F1-ATP synthase subunit alpha (ATP5A1)

Abstract

Most mitochondrial proteins are encoded by the nuclear genome, translated as precursor proteins in the cytosol and matured during directed import into the mitochondria 1. For many mitochondrial proteins this process is carefully regulated to meet demand and to avoid mitochondrial stress 2,3,4. Recently, mitochondrial F1-ATP synthase subunits have been found to interact with RNA across various eukaryotes. This includes genome wide RNA-interactome studies from yeast 5-7, fruit flies 8,9, plants 10-12, mice 13-17 and humans 18-24. To shed light on this unexpected observation, we determined the interacting cellular RNAs of ATP5A1 and the subcellular sites of interaction. Using RNA binding-deficient mutants of ATP5A1 and functional assays, we show that specific cytosolic RNAs bind ATP5A1 precursor proteins at the outer surface of mitochondria and promote their mitochondrial import both in vitro and in cellulo. These findings add an unexpected twist to understanding mitochondrial protein import and expand the growing list of riboregulated cellular processes.