title: Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy.
abstract: Mitochondrial fragmentation due to imbalanced fission and fusion of mitochondria is a prerequisite for mitophagy, however, the exact "coupling" of mitochondrial dynamics and mitophagy remains unclear. We have previously identified that FUNDC1 recruits MAP1LC3B/LC3B (LC3) through its LC3-interacting region (LIR) motif to initiate mitophagy in mammalian cells. Here, we show that FUNDC1 interacts with both DNM1L/DRP1 and OPA1 to coordinate mitochondrial fission or fusion and mitophagy. OPA1 interacted with FUNDC1 via its Lys70 (K70) residue, and mutation of K70 to Ala (A), but not to Arg (R), abolished the interaction and promoted mitochondrial fission and mitophagy. Mitochondrial stress such as selenite or FCCP treatment caused the disassembly of the FUNDC1-OPA1 complex while enhancing DNM1L recruitment to the mitochondria. Furthermore, we observed that dephosphorylation of FUNDC1 under stress conditions promotes the dissociation of FUNDC1 from OPA1 and association with DNM1L. Our data suggest that FUNDC1 regulates both mitochondrial fission or fusion and mitophagy and mediates the "coupling" across the double membrane for mitochondrial dynamics and quality control.
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Yueying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tan
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Chongzhuo
authors.initials: C
authors.lastname: Zhu
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.affiliation: c State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University , Tianjin , China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Han
authors.affiliation: c State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University , Tianjin , China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Chen
authors.affiliation: c State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University , Tianjin , China.
authors.forename: Ruize
authors.initials: R
authors.lastname: Gao
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: a State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences , Beijing , China.|b University of Chinese Academy of Sciences , Beijing , China.|c State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University , Tianjin , China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D047390:Casein Kinase II / Q000378:metabolism; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D063306:Mitophagy; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: C571016:FUNDC1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D047390:Casein Kinase II; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins
keywords: DNM1L/DRP1; OPA1; mitochondrial dynamics; mitophagy; mitophagy receptor