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

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  • Author(s): Li M;Li M;Li M; Jia J; Jia J; Jia J; Zhang X; Zhang X; Zhang X; Dai H; Dai H; Dai H
  • Source:
    Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2020 Sep 10; Vol. 530 (1), pp. 292-300. Date of Electronic Publication: 2020 Aug 06.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Mitophagy*; Apoptosis Regulatory Proteins/*metabolism ; Microtubule-Associated Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism; Apoptosis Regulatory Proteins/chemistry ; Binding Sites ; HEK293 Cells ; Humans ; Microtubule-Associated Proteins/chemistry ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Interaction Maps ; Proto-Oncogene Proteins c-bcl-2/chemistry
    • 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 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 significances, which will be helpful for future studies of mitophagy mediated by Bcl-rambo.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2020 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Bcl-rambo; LC3s/GABARAPs; Mitophagy; Selective binding
    • Accession Number:
      0 (Apoptosis Regulatory Proteins)
      0 (BCL2L13 protein, human)
      0 (GABARAP protein, human)
      0 (MAP1LC3A protein, human)
      0 (Microtubule-Associated Proteins)
      0 (Proto-Oncogene Proteins c-bcl-2)
    • Publication Date:
      Date Created: 20200824 Date Completed: 20210226 Latest Revision: 20210617
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbrc.2020.07.039
    • Accession Number:
      32828302