Graduate School of Frontier Biosciences, Osaka University

Japanese

Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling

Journal EMBO J, e201591440 (2015)
Authors Sakakibara K (1), Eiyama A (1), Suzuki SW (2), Sakoh-Nakatogawa M (3), Okumura N (4), Tani M (5), Hashimoto A (1), Nagumo S (1), Kondo-Okamoto N (1), Kondo-Kakuta C (3), Asai E (3), Kirisako H (3), Nakatogawa H (3), Kuge O (5), Takao T (4), Ohsumi Y (3), Okamoto K (6)

  1. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
  2. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan Frontier Research Center, Tokyo Institute of Technology, Kanagawa, Japan
  3. Frontier Research Center, Tokyo Institute of Technology, Kanagawa, Japan
  4. Institute for Protein Research, Osaka University, Osaka, Japan
  5. Department of Chemistry, Kyushu University, Fukuoka, Japan
  6. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
    kokamoto@fbs.osaka-u.ac.jp
Title Phospholipid methylation controls Atg32-mediated mitophagy and Atg8 recycling
PubMed 26438722
Laboratory Laboratory of Mitochondrial Dynamics 〈Assoc. Prof. Okamoto〉
Abstract Degradation of mitochondria via selective autophagy, termed mitophagy, contributes to mitochondrial quality and quantity control whose defects have been implicated in oxidative phosphorylation deficiency, aberrant cell differentiation, and neurodegeneration. How mitophagy is regulated in response to cellular physiology remains obscure. Here, we show that mitophagy in yeast is linked to the phospholipid biosynthesis pathway for conversion of phosphatidylethanolamine to phosphatidylcholine by the two methyltransferases Cho2 and Opi3. Under mitophagy-inducing conditions, cells lacking Opi3 exhibit retardation of Cho2 repression that causes an anomalous increase in glutathione levels, leading to suppression of Atg32, a mitochondria-anchored protein essential for mitophagy. In addition, loss of Opi3 results in accumulation of phosphatidylmonomethylethanolamine (PMME) and, surprisingly, generation of Atg8-PMME, a mitophagy-incompetent lipid conjugate of the autophagy-related ubiquitin-like modifier. Amelioration of Atg32 expression and attenuation of Atg8-PMME conjugation markedly rescue mitophagy in opi3-null cells. We propose that proper regulation of phospholipid methylation is crucial for Atg32-mediated mitophagy.