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Selective binding of mitophagy receptor protein Bcl-rambo to LC3/GABARAP family proteins.

Biochem Biophys Res Commun. 2020 Sep 10;530(1):292-300. Epub 2020 Aug 06
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摘要


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 Further investigations with bioinformatics analyses and mutagenesis suggested that the interactions with the HP1 and HP2 sites of LC3s/GABARAPs and the residues at the X2 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 significances, which will be helpful for future studies of mitophagy mediated by Bcl-rambo.

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原始数据


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