BCL2L13 is a mammalian homolog of the yeast mitophagy receptor Atg32.
Although Atg32 is essential for mitophagy in yeast, no mammalian homolog has been identified. Here, we demonstrate that BCL2L13 (BCL2-like 13 [apoptosis facilitator]) is a functional mammalian homolog of Atg32. First, we hypothesized that a mammalian mitophagy receptor will share certain molecular features with Atg32. Using the molecular profile of Atg32 as a search tool, we screened public databases for novel Atg32 functional homologs and identified BCL2L13. BCL2L13 induces mitochondrial fragmentation and mitophagy in HEK293 cells. In BCL2L13, the BH domains are important for fragmentation, whereas the WXXI motif, an LC3 interacting region, is needed for mitophagy. BCL2L13 induces mitochondrial fragmentation and mitophagy even in the absence of DNM1L/Drp1 and PARK2/Parkin, respectively. BCL2L13 is indispensable for mitochondrial damage-induced fragmentation and mitophagy. Furthermore, BCL2L13 induces mitophagy in Atg32-deficient yeast. Induction and/or phosphorylation of BCL2L13 may regulate its activity. Our findings thus open a new chapter in mitophagy research.
['Otsu|Kinya|K|', 'Murakawa|Tomokazu|T|', 'Yamaguchi|Osamu|O|']
D000818:Animals D001343:Autophagy D000071183:Autophagy-Related Proteins D006801:Humans D024101:Mitochondrial Proteins D063306:Mitophagy D019253:Proto-Oncogene Proteins c-bcl-2 D018160:Receptors, Cytoplasmic and Nuclear D029701:Saccharomyces cerevisiae Proteins D033921:Vesicular Transport Proteins
mitophagy Atg32 LC3 DNM1L PARK2 BCL2-like protein 13 mitochondrial fission