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

Dev Cell. 2018 Nov 5;47(3):281-293.e4. doi: 10.1016/j.devcel.2018.09.015. Epub 2018 Oct 11.

Abstract

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.

Keywords: Drosophila; autophagy; cell death; mTOR; monocarboxylate transporter; pyruvate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • HEK293 Cells / metabolism
  • Humans
  • Monocarboxylic Acid Transporters / metabolism
  • Proton Pumps
  • Protons
  • RNA-Binding Proteins / metabolism*
  • Salivary Glands / cytology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Drosophila Proteins
  • Monocarboxylic Acid Transporters
  • Proton Pumps
  • Protons
  • RNA-Binding Proteins
  • SLC16A11 protein, human
  • hrm protein, Drosophila
  • TOR Serine-Threonine Kinases