1. The Proton-Coupled Monocarboxylate Transporter Hermes Is Necessary for Autophagy during Cell Death
- Author
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Tsun-Kai Chang, William R. Kobertz, Eric H. Baehrecke, Panagiotis D. Velentzas, Charles Nelson, Gautam Das, and Lejie Zhang
- Subjects
0301 basic medicine ,Monocarboxylic Acid Transporters ,Programmed cell death ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Salivary Glands ,Article ,03 medical and health sciences ,Autophagy ,Animals ,Drosophila Proteins ,Humans ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Monocarboxylate transporter ,Cell growth ,TOR Serine-Threonine Kinases ,RNA-Binding Proteins ,Transporter ,Cell Biology ,Proton Pumps ,Phenotype ,Cell biology ,030104 developmental biology ,Drosophila melanogaster ,HEK293 Cells ,Cytoplasm ,biology.protein ,Protons ,Developmental Biology ,Signal Transduction - Abstract
Summary 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.
- Published
- 2018