A Mammalian Mitophagy Receptor, Bcl2-L-13, Recruits the ULK1 Complex to Induce Mitophagy

Tomokazu Murakawa,Koji Okamoto,Shigemiki Omiya,Manabu Taneike,Osamu Yamaguchi,Kinya Otsu

doi:10.1016/j.celrep.2018.12.050

Tomokazu Murakawa, Koji Okamoto + Show 4 more

Open Access

https://doi.org/10.1016/j.celrep.2018.12.050

Copy DOI

Journal: Cell Reports	Publication Date: Jan 1, 2019
Citations: 81	License type: cc-by

Affiliation: King's College London, Osaka University

Abstract

SummaryDegradation of mitochondria by selective autophagy, termed mitophagy, contributes to the control of mitochondrial quality. Bcl2-L-13 is a mammalian homolog of Atg32, which is an essential mitophagy receptor in yeast. However, the molecular machinery involved in Bcl2-L-13-mediated mitophagy remains to be elucidated. Here, we show that the ULK1 (unc-51-like kinase) complex is required for Bcl2-L-13 to process mitophagy. Screening of a series of yeast Atg mutants revealed that a different set of ATG genes is used for Bcl2-L-13- and Atg32-mediated mitophagy in yeast. The components of the Atg1 complex essential for starvation-induced autophagy were indispensable in Bcl2-L-13-, but not Atg32-mediated, mitophagy. The ULK1 complex, a counterpart of the Atg1 complex, is necessary for Bcl2-L-13-mediated mitophagy in mammalian cells. We propose a model where, upon mitophagy induction, Bcl2-L-13 recruits the ULK1 complex to process mitophagy and the interaction of LC3B with ULK1, as well as Bcl2-L-13, is important for the mitophagy.

Highlights

Autophagy is a nonselective degradation system for proteins and organelles induced upon starvation and conserved from yeast to mammals (Tanida, 2011)
Atg32, which is localized in the mitochondrial outer membrane, is a mitophagy receptor and interacts with Atg8, a ubiquitin-like protein conjugated to the lipid phosphatidylethanolamine through the WXXI motif (Kanki et al, 2009; Okamoto et al, 2009)
Bcl2-L-13 Requires Atg1, 13, 17, 29, and 31, but Not Atg11, to Induce Mitophagy in Yeast In this study, it was hypothesized that Bcl2-L-13 uses a similar molecular machinery to induce mitophagy in yeast and in mammalian cells, and a series of mutant yeasts was screened to identify necessary genes for Bcl2-L-13 to induce mitophagy in yeast

Summary

Introduction

Autophagy is a nonselective degradation system for proteins and organelles induced upon starvation and conserved from yeast to mammals (Tanida, 2011). Atg, which is localized in the mitochondrial outer membrane, is a mitophagy receptor and interacts with Atg, a ubiquitin-like protein conjugated to the lipid phosphatidylethanolamine through the WXXI motif (an Atg8interacting motif [AIM]) (Kanki et al, 2009; Okamoto et al, 2009). It interacts with Atg, a scaffolding protein, which recruits the core Atg protein assembly. We identified Bcl2-like protein 13 (Bcl2-L-13) as a mammalian functional homolog of Atg and found that it is essential for mitophagy in HEK293 cells (Murakawa et al, 2015)

Methods

Results

Conclusion