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

Cell Rep. 2019 Jan 8;26(2):338-345.e6. doi: 10.1016/j.celrep.2018.12.050.

Abstract

Degradation 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.

Keywords: Atg32; Bcl2-L-13; mitochondria; mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy-Related Protein-1 Homolog / metabolism*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mitophagy*
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Atg32 protein, S cerevisiae
  • Autophagy-Related Proteins
  • BCL2L13 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • ATG1 protein, S cerevisiae
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human