The ER membrane insertase Get1/2 is required for efficient mitophagy in yeast

Mashun Onishi; Sachiyo Nagumo; Shohei Iwashita; Koji Okamoto

doi:10.1016/j.bbrc.2018.04.114

The ER membrane insertase Get1/2 is required for efficient mitophagy in yeast

Biochem Biophys Res Commun. 2018 Sep 3;503(1):14-20. doi: 10.1016/j.bbrc.2018.04.114. Epub 2018 May 10.

Authors

Mashun Onishi¹, Sachiyo Nagumo¹, Shohei Iwashita¹, Koji Okamoto²

Affiliations

¹ Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
² Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: kokamoto@fbs.osaka-u.ac.jp.

PMID: 29673596
DOI: 10.1016/j.bbrc.2018.04.114

Abstract

Mitophagy is an evolutionarily conserved autophagy pathway that selectively eliminates mitochondria to control mitochondrial quality and quantity. Although mitophagy is thought to be crucial for cellular homeostasis, how this catabolic process is regulated remains largely unknown. Here we demonstrate that mitophagy during prolonged respiratory growth is strongly impaired in yeast cells lacking Get1/2, a transmembrane complex mediating insertion of tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane. Under the same conditions, loss of Get1/2 caused only slight defects in other types of selective and bulk autophagy. In addition, mitophagy and other autophagy-related processes are mostly normal in cells lacking Get3, a cytosolic ATP-driven chaperone that promotes delivery of TA proteins to the Get1/2 complex. We also found that Get1/2-deficient cells exhibited wildtype-like induction and mitochondrial localization of Atg32, a protein essential for mitophagy. Notably, Get1/2 is important for Atg32-independent, ectopically promoted mitophagy. Together, we propose that Get1/2-dependent TA protein(s) and/or the Get1/2 complex itself may act specifically in mitophagy.

Keywords: Autophagy; ER membrane insertase; Mitochondria; Yeast.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Vesicular Transport / genetics
Adaptor Proteins, Vesicular Transport / metabolism*
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Autophagy / physiology
Autophagy-Related Proteins / genetics
Autophagy-Related Proteins / metabolism
Endoplasmic Reticulum / metabolism
Gene Deletion
Genes, Fungal
Guanine Nucleotide Exchange Factors / genetics
Guanine Nucleotide Exchange Factors / metabolism
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Mitochondria / metabolism
Mitophagy / physiology*
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Red Fluorescent Protein
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*

Substances

ATG36 protein, S cerevisiae
Adaptor Proteins, Vesicular Transport
Atg32 protein, S cerevisiae
Autophagy-Related Proteins
GET1 protein, S cerevisiae
Get2 protein, S cerevisiae
Guanine Nucleotide Exchange Factors
Luminescent Proteins
Membrane Proteins
Receptors, Cytoplasmic and Nuclear
Saccharomyces cerevisiae Proteins
Adenosine Triphosphatases
Get3 protein, S cerevisiae