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Updated: May 19, 2026
Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
Published on: November 30, 2022
Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner
Magdalena Frank1, Stéphane Duvezin-Caubet, Sebastian Koob
1Adolf-Butenandt-Institut für Physiologische Chemie, Ludwig-Maximilians-Universität München, Germany.
Abstract:
Mitochondrial dysfunction is linked to apoptosis, aging, cancer, and a number of neurodegenerative and muscular disorders. The interplay between mitophagy and mitochondrial dynamics has been linked to the removal of dysfunctional mitochondria ensuring mitochondrial quality control. An open question is what role mitochondrial fission plays in the removal of mitochondria after mild and transient oxidative stress; conditions reported to result in moderately elevated reactive oxygen species (ROS) levels comparable to physical activity. Here we show that applying such conditions led to fragmentation of mitochondria and induction of mitophagy in mouse and human cells. These conditions increased ROS levels only slightly and neither triggered cell death nor led to a detectable induction of non-selective autophagy. Starvation led to hyperfusion of mitochondria, to high ROS levels, and to the induction of both non-selective autophagy and to a lesser extent to mitophagy. We conclude that moderate levels of ROS specifically trigger mitophagy but are insufficient to trigger non-selective autophagy. Expression of a dominant-negative variant of the fission factor DRP1 blocked mitophagy induction by mild oxidative stress as well as by starvation. Taken together, we demonstrate that in mammalian cells under mild oxidative stress a DRP1-dependent type of mitophagy is triggered while a concomitant induction of non-selective autophagy was not observed. We propose that these mild oxidative conditions resembling well physiological situations are thus very helpful for studying the molecular pathways governing the selective removal of dysfunctional mitochondria.
Insights
Mild oxidative stress, similar to exercise, triggers selective mitochondrial removal (mitophagy) via DRP1 in cells. This process, unlike starvation, does not induce general autophagy and avoids cell death, highlighting a specific pathway for mitochondrial quality control.
Area of Science:
- Cell Biology
- Mitochondrial Biology
- Autophagy Research
Background:
- Mitochondrial dysfunction is implicated in aging, cancer, and neurodegenerative diseases.
- Mitophagy and mitochondrial dynamics are crucial for maintaining mitochondrial quality control.
- The role of mitochondrial fission in removing damaged mitochondria under mild stress is not well understood.
Purpose of the Study:
- To investigate the role of mitochondrial fission in mitophagy under mild oxidative stress.
- To differentiate the cellular response to mild oxidative stress from starvation regarding autophagy and mitophagy.
- To elucidate the molecular pathways involved in selective mitochondrial removal.
Main Methods:
- Induction of mild oxidative stress in mouse and human cells.
- Analysis of mitochondrial morphology (fission/fusion) and mitophagy markers.
- Assessment of reactive oxygen species (ROS) levels and cell death.
- Investigation of autophagy induction (non-selective and selective).
- Use of dominant-negative DRP1 to inhibit mitochondrial fission.
Main Results:
- Mild oxidative stress induced mitochondrial fragmentation and mitophagy without significant ROS increase or cell death.
- Non-selective autophagy was not induced by mild oxidative stress, distinguishing it from starvation.
- Starvation led to mitochondrial hyperfusion, high ROS, and induced both non-selective autophagy and mitophagy.
- DRP1 inhibition blocked mitophagy induction under both mild oxidative stress and starvation.
- Moderate ROS levels specifically trigger mitophagy, not general autophagy.
Conclusions:
- Mild oxidative stress selectively triggers DRP1-dependent mitophagy in mammalian cells.
- This selective mitophagy pathway is distinct from non-selective autophagy induced by starvation.
- These findings provide insights into mitochondrial quality control mechanisms under physiological conditions.
- Mild oxidative stress conditions are valuable for studying selective mitochondrial removal pathways.
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