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Updated: Oct 1, 2025

Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
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Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples

Published on: May 10, 2015

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The Mitochondrial Deubiquitinase USP30 Regulates AKT/mTOR Signaling

Ruohan Zhang1,2, Serra Ozgen1, Hongke Luo1

  • 1Department of Physiology and Cell Biology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Frontiers in Pharmacology
|March 7, 2022
PubMed

Insights

Parkin and USP30 regulate cell death pathways by controlling AKT/mTOR signaling during mitophagy. Parkin promotes apoptosis, while USP30 inhibits it, offering potential cancer treatment strategies.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitophagy maintains mitochondrial health by removing damaged mitochondria.
  • Parkin and USP30 are key regulators of mitophagy, with Parkin initiating and USP30 antagonizing the process.
  • The AKT/mTOR signaling pathway is crucial for cell growth and survival, and its link to mitophagy is under investigation.

Purpose of the Study:

  • To investigate the specific mechanisms by which Parkin and USP30 regulate AKT/mTOR signaling during mitophagy.
  • To elucidate the roles of Parkin and USP30 in apoptosis.
  • To explore potential therapeutic strategies targeting USP30 in cancer treatment.

Main Methods:

  • Utilized a set of genetic reagents to study Parkin and USP30.
  • Investigated the regulation of AKT/mTOR signaling under conditions of mitochondrial stress.
  • Analyzed the impact of Parkin and USP30 on apoptosis.

Main Results:

  • Parkin inhibits AKT/mTOR signaling following mitochondrial stress, promoting apoptosis.
  • USP30 overexpression counteracts Parkin's activity, sustaining AKT/mTOR activity and inhibiting apoptosis.
  • AKT/mTOR signaling is regulated by Parkin and USP30 activity during mitophagy.

Conclusions:

  • Parkin and USP30 play critical roles in regulating apoptosis through the AKT/mTOR signaling pathway.
  • USP30 inhibition may enhance the efficacy of AKT/mTOR inhibitors in cancer therapy.
  • Findings offer new insights into the interplay between mitophagy regulators and cell death pathways.
Keywords:
USP30aktcancerleukemiamTORmitophagyparkin

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