title: COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1.
abstract: Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology.
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Ban-Ishihara
authors.affiliation: Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Tomohiro-Takamiya
authors.affiliation: Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tani
authors.affiliation: INSERM, Unité 873, Grenoble F-38054, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Baudier
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan. Electronic address: ishihara_naotada@kurume-u.ac.jp.
authors.forename: Naotada
authors.initials: N
authors.lastname: Ishihara
authors.affiliation: Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan. Electronic address: kuge@chem.kyushu-univ.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kuge
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D053142:Mitochondrial Size / Q000235:genetics*; D008969:Molecular Sequence Data; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D000097573:Red Fluorescent Protein
chemical_list: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D034281:Dynamins; D020558:GTP Phosphohydrolases; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D000097573:Red Fluorescent Protein; C549686:ATAD3A protein, human; C578539:COA3 protein, human; C110768:DNM1L protein, human
keywords: Cytochrome oxidase (COX); Drpl; Mitochondria; Mitochondrial fission; Organelle