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.


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
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid


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