TMP21 regulates autophagy by modulating ROS production and mTOR activation

Biochem Biophys Res Commun. 2019 Oct 22;518(4):746-751. doi: 10.1016/j.bbrc.2019.08.125. Epub 2019 Aug 28.

Abstract

Autophagy is a catabolic cellular response to stress that has been liked to various human diseases. However, the precise involvement of autophagy in health and disease remains unclear. To explore the molecular mechanisms of autophagy, we investigated the effect of TMP21. We found that the down-regulation of TMP21 induced autophagy in SH-SY5Y cells. In addition, the enhanced autophagy observed upon TMP21 depletion was almost completely blocked in ATG5 knockout (KO) or ATG7-KO HeLa cells. Silencing of TMP21 in SH-SY5Y cells also increased the production of cellular reactive oxygen species (ROS). Accordingly, treatment with the ROS scavenger NAC suppressed autophagy activation as well as ROS production in TMP21-depleted cells. In addition, the inhibition of mTOR by treatment with Torin1 was mitigated in TMP21 overexpressing cells compared with that in control cells. Taken together, these results indicated that TMP21 could regulate autophagy by modulating ROS production and mTOR activation.

Keywords: Autophagy; ROS; TMP21; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Autophagy / genetics*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / metabolism
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockout Techniques
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Naphthyridines / pharmacology
  • Nucleocytoplasmic Transport Proteins
  • RNA Interference
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Membrane Proteins
  • Naphthyridines
  • Nucleocytoplasmic Transport Proteins
  • Reactive Oxygen Species
  • TMED10 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ATG7 protein, human
  • Autophagy-Related Protein 7
  • Acetylcysteine