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Functionally conserved inner mitochondrial membrane proteins CCDC51 and Mdm33 demarcate a subset of fission events

Alia R Edington1, Olivia M Connor1, Abigail C Love1

  • 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

The Journal of Cell Biology
|December 24, 2024
PubMed

Insights

Internal mitochondrial proteins, like human CCDC51, directly regulate mitochondrial fission. This study identifies a conserved protein involved in mitochondrial dynamics and fragmentation.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Protein Function

Background:

  • Mitochondrial fission is crucial for cellular health, but the role of internal mitochondrial proteins is not well understood.
  • The yeast protein Mdm33 is implicated in mitochondrial morphology, yet its direct function and mammalian homologs were unknown.

Purpose of the Study:

  • To investigate the role of internal mitochondrial proteins in metazoan mitochondrial fission.
  • To identify and characterize a human ortholog of the yeast Mdm33 protein.

Main Methods:

  • Bioinformatic analysis to identify structural orthologs.
  • Gene knockdown experiments to assess protein function.
  • Confocal microscopy for spatial and temporal localization.
  • Overexpression studies to determine effects on mitochondrial fragmentation.

Main Results:

  • A human ortholog of Mdm33, CCDC51 (MITOK), was identified.
  • CCDC51 depletion phenocopied Mdm33 loss, reducing mitochondrial fission rates.
  • CCDC51 was localized to specific mitochondrial fission events and associated with Drp1 upon overexpression, inducing fragmentation.

Conclusions:

  • Mdm33 and CCDC51 are functionally conserved regulators of mitochondrial fission.
  • Internal mitochondrial proteins directly participate in mitochondrial fission events in human cells.

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