title: Mitofusin 1 inhibits an apoptosis-associated amino-terminal conformational change in Bax, but not its mitochondrial translocation, in a GTPase-dependent manner.
abstract: Mitochondrial fusion and fission are dynamically regulated during apoptotic cell death, and mitofusin (Mfn) and related proteins have been shown to be involved in apoptosis-associated changes in mitochondrial morphology and function. Here, we investigated the involvement of Mfn proteins in the conformational activation and mitochondrial translocation of Bax, a key molecule responsible for apoptosis-associated mitochondrial changes. When ectopically expressed, Mfn1 inhibited the amino-terminal activation, but not the mitochondrial translocation, of Bax during staurosporine-induced apoptosis; overexpression of Mfn2 had no effect. Overexpression of Mfn1 mutants carrying point mutations in the GTPase domain (Mfn1-K88T and Mfn1-T109A) did not inhibit the amino-terminal activation of Bax. Furthermore, staurosporine-induced amino-terminal activation of Bax was significantly delayed in Mfn1-shRNA transfected (Mfn1-depleted) HeLa cells compared to cells transfected with control shRNA. These results collectively suggest a role for Mfn1 in regulating the activation of Bax on the outer mitochondrial membrane in a GTPase-dependent manner.
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Republic of Korea; KI for the Bio Century, KAIST, Daejeon 305-701, Republic of Korea. Electronic address: ryus@kaist.ac.kr.
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Ryu
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Republic of Korea.
authors.forename: Kyungsun
authors.initials: K
authors.lastname: Choi
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-711, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-770, Republic of Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: KI for the Bio Century, KAIST, Daejeon 305-701, Republic of Korea; Department of Biological Sciences, KAIST, Daejeon 305-701, Republic of Korea.
authors.forename: Sunchang
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, KAIST, Daejeon 305-701, Republic of Korea; KI for the Bio Century, KAIST, Daejeon 305-701, Republic of Korea. Electronic address: cchoi@kaist.ac.kr.
authors.forename: Chulhee
authors.initials: C
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D051028:bcl-2-Associated X Protein; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human