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Updated: Jun 21, 2026
07:20
Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
The pyruvate transporter hermes regulates autophagy and health by modulating ROS production
Panagiotis D Velentzas1, Fei Chai1, Eric H Baehrecke1
1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Cell Reports
|June 19, 2026
Summary
The plasma membrane pyruvate carrier hermes (hrm) regulates autophagy and mTOR signaling. Loss of hrm impairs mitochondrial pyruvate metabolism, increasing reactive oxygen species (ROS) and decreasing lifespan.
Area of Science:
- Cellular Biology
- Metabolic Pathways
- Molecular Genetics
Background:
- Autophagy is a vital cellular process for degrading waste, regulated by nutrient signaling pathways like mTOR.
- The plasma membrane pyruvate transporter hermes (hrm) plays a role in developmental autophagy and mTOR signaling.
- Understanding the precise mechanisms linking nutrient transport to autophagy is crucial for cellular health.
Purpose of the Study:
- To identify genes influencing pyruvate metabolism that can rescue the autophagy defects caused by hrm loss.
- To elucidate the role of mitochondrial pyruvate transport and the Krebs cycle in hrm-mediated autophagy regulation.
- To investigate the connection between hrm, reactive oxygen species (ROS) production, and organismal health.
Main Methods:
- Genetic screening for suppressors of the hrm mutant phenotype.
- Analysis of pyruvate transport into mitochondria and its impact on the Krebs cycle.
- Measurement of reactive oxygen species (ROS) levels in hrm mutants.
- Assessment of autophagy and mTOR signaling pathway activation.
- Evaluation of lifespan and intestinal autophagy in adult hrm mutant animals.
Main Results:
- Loss of hrm function inhibits autophagy, dependent on mitochondrial pyruvate transport and Krebs cycle activity.
- hrm deficiency leads to increased ROS production, which is sufficient to reverse autophagy and mTOR signaling defects.
- Adult hrm mutants exhibit a reduced lifespan and impaired intestinal autophagy.
- A direct link was established between a plasma membrane pyruvate carrier and mitochondrial metabolism, ROS, and autophagy.
Conclusions:
- The plasma membrane pyruvate carrier hrm is critical for linking pyruvate metabolism to mitochondrial function, ROS homeostasis, and autophagy.
- Disruption of hrm impacts organismal health, evidenced by decreased lifespan and intestinal autophagy defects.
- This study highlights a novel regulatory axis involving pyruvate transport, mitochondrial activity, and cellular stress responses in maintaining health.
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