COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1

Reiko Ban-Ishihara; Shiho Tomohiro-Takamiya; Motohiro Tani; Jacques Baudier; Naotada Ishihara; Osamu Kuge

doi:10.1016/j.febslet.2015.08.039

COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1

FEBS Lett. 2015 Oct 7;589(20 Pt B):3126-32. doi: 10.1016/j.febslet.2015.08.039. Epub 2015 Sep 7.

Authors

Reiko Ban-Ishihara¹, Shiho Tomohiro-Takamiya², Motohiro Tani², Jacques Baudier³, Naotada Ishihara⁴, Osamu Kuge⁵

Affiliations

¹ Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan.
² Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan.
³ INSERM, Unité 873, Grenoble F-38054, France.
⁴ Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume 839-0864, Japan. Electronic address: ishihara_naotada@kurume-u.ac.jp.
⁵ Department of Chemistry, Faculty of Sciences, Kyushu University, Fukuoka 812-8581, Japan. Electronic address: kuge@chem.kyushu-univ.jp.

PMID: 26358295
DOI: 10.1016/j.febslet.2015.08.039

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.

Keywords: Cytochrome oxidase (COX); Drpl; Mitochondria; Mitochondrial fission; Organelle.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATPases Associated with Diverse Cellular Activities
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Amino Acid Sequence
Dynamins
GTP Phosphohydrolases / genetics*
GTP Phosphohydrolases / metabolism
HeLa Cells
Humans
Immunoblotting
Luminescent Proteins / genetics
Luminescent Proteins / metabolism
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Microscopy, Confocal
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Mitochondria / genetics
Mitochondria / metabolism
Mitochondrial Dynamics / genetics
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Mitochondrial Size / genetics*
Molecular Sequence Data
Protein Binding
RNA Interference
Red Fluorescent Protein
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid

Substances

ATAD3A protein, human
COA3 protein, human
Luminescent Proteins
Membrane Proteins
Microtubule-Associated Proteins
Mitochondrial Proteins
Adenosine Triphosphatases
GTP Phosphohydrolases
ATPases Associated with Diverse Cellular Activities
DNM1L protein, human
Dynamins