Lysosomes: Signaling Hubs for Metabolic Sensing and Longevity

Trends Cell Biol. 2019 Nov;29(11):876-887. doi: 10.1016/j.tcb.2019.08.008. Epub 2019 Oct 11.

Abstract

Lysosomes are sites of active metabolism in a cell. They contain various hydrolases that degrade extracellular and intracellular materials during endocytosis and autophagy, respectively. In addition to their long-recognized roles in degradation and recycling, emerging studies have revealed that lysosomes are organizing centers for signal transduction. Lysosome-derived signaling plays crucial roles in regulating nutrient sensing, metabolic adaptation, organelle crosstalk, and aging. In particular, how the degradative role of the lysosome cooperates with its signaling functions to actively modulate lifespan is beginning to be unraveled. This review describes recent advances in the role of the lysosome as a 'signaling hub' that uses three different lysosome-derived signaling pathways to integrate metabolic inputs, organelle interactions, and the control of longevity.

Keywords: AMPK signaling; aging and longevity; lipid messenger signaling; lysosome-to-nucleus signaling; mTOR signaling.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Autophagy / physiology*
  • Endocytosis / physiology*
  • Humans
  • Longevity / physiology
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mitochondria / metabolism
  • Signal Transduction / physiology*

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • AMP-Activated Protein Kinases