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.
a Cardiovascular Division; King's College London British Heart Foundation Centre of Excellence ; London , United Kingdom.
Kinya
K
Otsu
b Department of Cardiovascular Medicine, Graduate School of Medicine; Osaka University ; Suita , Osaka , Japan.
Tomokazu
T
Murakawa
b Department of Cardiovascular Medicine, Graduate School of Medicine; Osaka University ; Suita , Osaka , Japan.
Osamu
O
Yamaguchi
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism*; D063306:Mitophagy / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
C543183:Atg32 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; C431152:BCL2L13 protein, human; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins
Atg32; BCL2-like protein 13; DNM1L; LC3; PARK2; mitochondrial fission; mitophagy