The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins

Mol Biol Cell. 2021 Apr 15;32(8):664-674. doi: 10.1091/mbc.E20-11-0748. Epub 2021 Feb 17.

Abstract

For the biogenesis of mitochondria, hundreds of proteins need to be targeted from the cytosol into the various compartments of this organelle. The intramitochondrial targeting routes these proteins take to reach their respective location in the organelle are well understood. However, the early targeting processes, from cytosolic ribosomes to the membrane of the organelle, are still largely unknown. In this study, we present evidence that an integral membrane protein of the endoplasmic reticulum (ER), Ema19, plays a role in this process. Mutants lacking Ema19 show an increased stability of mitochondrial precursor proteins, indicating that Ema19 promotes the proteolytic degradation of nonproductive precursors. The deletion of Ema19 improves the growth of respiration-deficient cells, suggesting that Ema19-mediated degradation can compete with productive protein import into mitochondria. Ema19 is the yeast representative of a conserved protein family. The human Ema19 homologue is known as sigma 2 receptor or TMEM97. Though its molecular function is not known, previous studies suggested a role of the sigma 2 receptor as a quality control factor in the ER, compatible with our observations about Ema19. More globally, our data provide an additional demonstration of the important role of the ER in mitochondrial protein targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytosol / metabolism
  • Endoplasmic Reticulum / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Proteins / metabolism
  • Protein Transport
  • Proteolysis
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Membrane Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • Saccharomyces cerevisiae Proteins