Parkin-mediated ubiquitination contributes to the constitutive turnover of mitochondrial fission factor (Mff)

Laura Lee1, Richard Seager1, Yasuko Nakamura1

  • 1School of Biochemistry, Centre for Synaptic Plasticity, Biomedical Sciences Building, University of Bristol, Bristol, United Kingdom.

Plos One
|May 22, 2019
PubMed

Insights

Parkin ubiquitinates Mitochondrial Fission Factor (Mff) even in unstressed cells, revealing a new role in maintaining mitochondrial health. This constitutive turnover is crucial for mitochondrial proteostasis.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Protein Degradation

Background:

  • Mitochondrial Fission Factor (Mff) is critical for mitochondrial fission.
  • PINK1/Parkin pathway targets Mff for mitophagy in stressed mitochondria.
  • The role of Mff ubiquitination in non-stressed conditions is unclear.

Purpose of the Study:

  • To investigate the role of Parkin in Mff ubiquitination under non-stressed conditions.
  • To identify ubiquitin ligases involved in constitutive Mff turnover.
  • To elucidate the function of Mff ubiquitination in physiological mitochondrial maintenance.

Main Methods:

  • PINK1 and Parkin expression analysis.
  • Mff ubiquitination assays.
  • shRNA-mediated knockdown of Parkin.
  • Mitochondrial proteostasis assessment.

Main Results:

  • Parkin ubiquitinates Mff in a PINK1-dependent manner under non-stressed conditions.
  • Parkin regulates constitutive Mff turnover, independent of mitophagy.
  • Parkin knockdown does not abolish Mff ubiquitination, suggesting other ligases are involved.
  • Mff ubiquitination contributes to physiological mitochondrial membrane protein composition.

Conclusions:

  • Parkin plays a role in the physiological maintenance of Mff levels in unstressed cells.
  • Constitutive Mff ubiquitination by Parkin is a key mechanism for mitochondrial proteostasis.
  • Additional ubiquitin ligases contribute to Mff turnover, highlighting complex regulatory networks.

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