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Updated: Oct 5, 2025
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Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
Published on: August 12, 2018
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Negative feedback system to maintain cell ROS homeostasis: KEAP1-PGAM5 complex senses mitochondrially generated ROS
Akbar Zeb1, Vinay Choubey1, Ruby Gupta1
1Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Autophagy
|January 29, 2022
Summary
Cells remove faulty mitochondria when reactive oxygen species (ROS) overwhelm antioxidant defenses. Moderate ROS breaks the KEAP1-PGAM5 complex, leading to PGAM5 accumulation and mitochondrial autophagy to maintain cell ROS homeostasis.
Area of Science:
- Cellular Biology
- Mitochondrial Dynamics
- Oxidative Stress
Background:
- Cellular reactive oxygen species (ROS) production can exceed antioxidant capacity, disrupting ROS homeostasis.
- Faulty mitochondria are a primary source of excessive ROS and require removal to maintain cellular health.
Purpose of the Study:
- To investigate the molecular mechanisms by which cells eliminate ROS-producing mitochondria.
- To elucidate the role of the KEAP1-PGAM5 complex and PGAM5 accumulation in mitochondrial quality control.
Main Methods:
- Investigated the effect of ROS on the KEAP1-PGAM5 complex.
- Assessed the impact of PGAM5 accumulation on PINK1 processing.
- Examined the role of PGAM5 in sensitizing mitochondria to autophagic removal.
Main Results:
- Moderate ROS production disrupts the KEAP1-PGAM5 complex, preventing proteasomal degradation of PGAM5.
- Accumulated PGAM5 interferes with PINK1 processing.
- This interference sensitizes mitochondria to autophagic removal, a process known as mitophagy.
Conclusions:
- A negative feedback system involving PGAM5 accumulation and mitochondrial autophagy is proposed.
- This mechanism actively maintains cellular ROS homeostasis by eliminating dysfunctional mitochondria.
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