title: Drp1, Mff, Fis1, and MiD51 are coordinated to mediate mitochondrial fission during UV irradiation-induced apoptosis.
abstract: Mitochondrial fission and proteins vital to this process play essential roles in apoptosis. Several mitochondrial outer membrane proteins, including mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (Mff) and mitochondrial dynamics of 51 kDa protein (MiD51), also known as mitochondrial elongation factor 1 (MEIF1), have been reported to promote mitochondrial fission by recruiting the GTPase dynamin-related protein 1 (Drp1). However, it remains unclear how these fission factors coordinate to control apoptotic mitochondrial fission. Molecular studies have suggested the existence of interaction between Mff and Drp1, but fundamental questions remain concerning their function. In the present study, we reported that the phosphorylation status of Drp1-Ser(637) was essential for its interaction with Mff. UV stimulation induced a decrease in cytoplasmic and mitochondrial Drp1 phosphorylation on Ser(637) and enhanced the interaction between Drp1 and Mff, resulting in mitochondrial fragmentation. Simultaneously, the interaction increased markedly between Fis1 and MiD51/MIEF1, whereas the interaction between Drp1 and MiD51/MIEF1 decreased significantly after UV irradiation, which suggests that Fis1 competitively binds to MiD51/MIEF1 to activate Drp1 indirectly. Moreover, Mff-Drp1 binding and Mff-mediated recruitment of Drp1 to mitochondria did not require Bax during UV stimulation. Our study revealed a novel role of Mff in regulation of mitochondrial fission and showed how the fission proteins are orchestrated to mediate the fission process during apoptosis.
authors.affiliation: Ministry of Education Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Ministry of Education Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Ministry of Education Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China xingda@scnu.edu.cn.
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D014466:Ultraviolet Rays
chemical_list: C476525:FIS1 protein, human; C561316:MIEF1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010445:Peptide Elongation Factors; D034281:Dynamins
keywords: Bax; GTP-binding; MIEF1; mitochondrial fragmentation; oligomerization