The pyruvate transporter hermes regulates autophagy and health by modulating ROS production
Autophagy is a catabolic process that degrades cytoplasmic materials and is controlled by nutrient availability and signaling. The plasma membrane-associated pyruvate-solute carrier hermes (hrm) is required for regulation of the mechanistic target of rapamycin (mTOR) signaling and the activation of autophagy during development. Here, we screen for pyruvate-influencing genes that suppress the hrm mutant phenotype. We show that the inhibitory effect of hrm loss on autophagy depends on pyruvate transport into mitochondria and the Krebs cycle. Loss of hrm results in an increase in reactive oxygen species (ROS), and attenuation of the increase in ROS is sufficient to suppress the effects of hrm loss on autophagy and mTOR signaling. Importantly, we show that in adult animals, loss of hrm results in decreased lifespan, with defects in autophagy in intestine tissues. These results link a plasma membrane pyruvate carrier to mitochondrial pyruvate metabolism, ROS, autophagy, and organismal health.
Authors
- Panagiotis D. Velentzas (ORCID: https://orcid.org/0000-0001-9552-8403)
- Eric H. Baehrecke (ORCID: https://orcid.org/0000-0003-1683-5064)
- Fei Chai (ORCID: https://orcid.org/0000-0002-6718-441X)
Institutions
- University of Massachusetts Chan Medical School (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-06-19
- DOI
- https://doi.org/10.1016/j.celrep.2026.117574
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute on Aging
- National Institute of General Medical Sciences