Lysosome: regulator of lipid degradation pathways

Trends Cell Biol. 2014 Dec;24(12):743-50. doi: 10.1016/j.tcb.2014.06.006. Epub 2014 Jul 21.

Abstract

Autophagy is a catabolic pathway that has a fundamental role in the adaptation to fasting and primarily relies on the activity of the endolysosomal system, to which the autophagosome targets substrates for degradation. Recent studies have revealed that the lysosomal-autophagic pathway plays an important part in the early steps of lipid degradation. In this review, we discuss the transcriptional mechanisms underlying co-regulation between lysosome, autophagy, and other steps of lipid catabolism, including the activity of nutrient-sensitive transcription factors (TFs) and of members of the nuclear receptor family. In addition, we discuss how the lysosome acts as a metabolic sensor and orchestrates the transcriptional response to fasting.

Keywords: Autophagy; FOXOs; TFEB; TP53; lipophagy; lysosome; mTORC1; nuclear receptors; transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autophagy / genetics*
  • Fasting / metabolism
  • Humans
  • Lipid Metabolism / genetics*
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Phagosomes / genetics*
  • Phagosomes / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Multiprotein Complexes
  • Receptors, Cytoplasmic and Nuclear
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1