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Dual role of USP30 in controlling basal pexophagy and mitophagy

Elena Marcassa1, Andreas Kallinos1, Jane Jardine1

  • 1Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

EMBO Reports
|June 14, 2018
PubMed

Insights

Ubiquitin-specific protease 30 (USP30) protein suppresses mitophagy and pexophagy, crucial cellular clearance pathways. USP30 regulates both PINK1-dependent and independent selective autophagy, impacting reactive oxygen species (ROS) levels.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • USP30 is an outer mitochondrial membrane protein.
  • It counteracts PINK1/Parkin-dependent mitophagy.
  • Mitophagy is essential for clearing damaged mitochondria.

Purpose of the Study:

  • To investigate USP30's role in basal mitophagy.
  • To explore USP30's function in Parkin-deficient cells.
  • To determine USP30's involvement in peroxisome clearance (pexophagy).

Main Methods:

  • Utilized two distinct mitophagy reporter systems.
  • Analyzed USP30 localization in mammalian cells.
  • Investigated PINK1 and Parkin-independent pathways.

Main Results:

  • USP30 tonically suppresses a PINK1-dependent mitophagy component.
  • USP30 acts upstream of PINK1, modulating substrate availability.
  • A fraction of USP30 targets peroxisomes, regulating pexophagy independently of PINK1/Parkin.

Conclusions:

  • USP30 plays a critical role in clearing major reactive oxygen species (ROS) sources.
  • USP30 regulates both PINK1-dependent mitophagy and PINK1-independent pexophagy.
  • USP30 is a key regulator of selective autophagy pathways.
Keywords:
PINK1USP30mitochondriamitophagyperoxisomesubiquitin

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