期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 530, 期 1, 页码 292-300出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2020.07.039
关键词
Bcl-rambo; LC3s/GABARAPs; Mitophagy; Selective binding
资金
- National Natural Science Foundation of China [21703254, 21772201]
- Second Affiliated Hospital of Anhui Medical University
- Center of Medical Physics and Technology [LHJJ202006, LHJJ202007]
Mitophagy regulates the metabolic level and cell fates by specifically degrading damaged or redundant mitochondria in these cells. During the formation of autophagosomes, autophagy receptors and adaptors, which usually contain a LC3-interacting region (LIR) domain, are recruited through their interactions with LC3/GABARAP family of proteins. Bcl-rambo is one of the mitophagy receptors that interact with LC3s/GABARAPs. In this study, we first measured the binding of Bcl-rambo to LC3s/GABARAPs in vitro and found Bcl-rambo has a selectivity to LC3C/GABARP/GABARAPL1. Further investigations with bioinfor-matics analyses and mutagenesis suggested that the interactions with the HP1 and HP2 sites of LC3s/GABARAPs and the residues at the X-2 site of the LIR domain of Bcl-rambo are both critical for the selectivity. Moreover, assays in vivo showed that manipulating the selective binding of Bcl-rambo resulted in the changes of mitophagy inductions in the cells. Overall, our data revealed the selective binding between Bcl-rambo and LC3s/GABARAPs and its molecular mechanisms and biological signifi-cances, which will be helpful for future studies of mitophagy mediated by Bcl-rambo. (C) 2020 Elsevier Inc. All rights reserved.
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