The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death

Nutrient availability influences the production and degradation of materials that are required for cell growth and survival. Autophagy is a nutrient-regulated process that is used to degrade cytoplasmic materials and has been associated with human diseases. Solute transporters influence nutrient availability and sensing, yet we know little about how transporters influence autophagy. Here, we screen for solute transporters that are required for autophagy-dependent cell death and identify CG11665/hermes. We show that hermes is required for both autophagy during steroid-triggered salivary gland cell death and TNF-induced non-apoptotic eye cell death. hermes encodes a proton-coupled monocarboxylate transporter that preferentially transports pyruvate over lactate. mTOR signaling is elevated in hermes mutant cells, and decreased mTOR function suppresses the hermes salivary gland cell death phenotype. Hermes is most similar to human SLC16A11, a protein that was recently implicated in type 2 diabetes, thus providing a link between pyruvate, mTOR, autophagy, and possibly metabolic disorders. [Display omitted] •Members of the SLC superfamily are required for cell death during development•Identification of hermes, a gene that is required for autophagy during cell death•Hermes is a proton-coupled pyruvate transporter•Hermes influences mTOR to regulate autophagy Velentzas et al. identify a requirement for the pyruvate transporter Hermes in autophagy that is associated with cell death in Drosophila. Hermes influences mTOR signaling and is similar to the type 2 diabetes-associated human protein SLC16A11, thus suggesting a further link between autophagy and metabolic disorders.