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

  • Biochem Biophys Res Commun. 2020 Sep 10;530(1):292-300. doi: 10.1016/j.bbrc.2020.07.039.
Mengqing Li  1 ,  Jia Jia  2 ,  Xuecheng Zhang  3 ,  Haiming Dai  4
Affiliations
  • 1. School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Anhui Provincial Engineering Technology Research Center of Microorganisms and Biocatalysis, Hefei, Anhui, 230601, China.
  • 2. Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, China; Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, China.
  • 3. School of Life Sciences, Anhui University, Hefei, Anhui, 230601, China; Anhui Provincial Engineering Technology Research Center of Microorganisms and Biocatalysis, Hefei, Anhui, 230601, China. Electronic address: [email protected].
  • 4. Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, Anhui, 230031, China; Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, 230031, China. Electronic address: [email protected].
PMID: 32828302 DOI: 10.1016/j.bbrc.2020.07.039
Abstract

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 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.

Keywords
Bcl-rambo; LC3s/GABARAPs; Mitophagy; Selective binding.
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