Endophilin B2 promotes inner mitochondrial membrane degradation by forming heterodimers with Endophilin B1 during mitophagy.
Mitochondrial sequestration by autophagosomes is a key step in mitophagy while the mechanisms mediating this process are not fully understood. It has been reported that Endophilin B1 (EB1) promotes mitochondrial sequestration by binding and shaping membrane. However, the role of EB1 homolog Endophilin B2 (EB2) in mitophagy remains unclear. Here we report that EB2 plays an indispensable role in mitochondria sequestration and inner mitochondrial membrane (IMM) protein degradation during mitophagy. Similar to EB1, EB2 aggregates into foci and then translocates to damaged mitochondria. Loss of either EB2 and/or EB1 significantly enervates the foci translocation to fragmented mitochondria and IMM degradation, and the EB1/EB2 heterodimer formed by EB1/EB2 interaction promotes the above process. We noticed that, it is the dimer domain of EB2 but not that of EB1 mediating the heterodimer formation, manifesting the importance of EB2 in mitophagy. Furthermore, we demonstrate that the EB foci formation is closely regulated by the PINK1-Parkin signaling pathway. From these results, we propose that EB1/EB2 heterodimers may serve as linkers between damaged mitochondria and phagophores during mitophagy.
University of Chinese Academy of Sciences, Beijing 100049, China.|State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Yi-Han
YH
Wang
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Jiu-Qiang
JQ
Wang
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Qiaochu
Q
Wang
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Yun
Y
Wang
Key Laboratory of Genomic and Precision Medicine, China Gastrointestinal Cancer Research Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Caixia
C
Guo
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Quan
Q
Chen
University of Chinese Academy of Sciences, Beijing 100049, China.
Tuanyao
T
Chai
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Tie-Shan
TS
Tang
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism*; D063306:Mitophagy; D059748:Proteolysis
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; C429293:SH3GLB1 protein, human; C486098:SH3GLB2 protein, human