Autophagy, lipophagy and lysosomal lipid storage disorders

Biochim Biophys Acta. 2016 Apr;1861(4):269-84. doi: 10.1016/j.bbalip.2016.01.006. Epub 2016 Jan 14.

Abstract

Autophagy is a catabolic process with an essential function in the maintenance of cellular and tissue homeostasis. It is primarily recognised for its role in the degradation of dysfunctional proteins and unwanted organelles, however in recent years the range of autophagy substrates has also been extended to lipids. Degradation of lipids via autophagy is termed lipophagy. The ability of autophagy to contribute to the maintenance of lipo-homeostasis becomes particularly relevant in the context of genetic lysosomal storage disorders where perturbations of autophagic flux have been suggested to contribute to the disease aetiology. Here we review recent discoveries of the molecular mechanisms mediating lipid turnover by the autophagy pathways. We further focus on the relevance of autophagy, and specifically lipophagy, to the disease mechanisms. Moreover, autophagy is also discussed as a potential therapeutic target in several key lysosomal storage disorders.

Keywords: Autophagy; Lipid metabolism; Lipid storage disorders.

Publication types

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

MeSH terms

  • Animals
  • Autophagy* / genetics
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Humans
  • Lipid Metabolism* / genetics
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipid Metabolism, Inborn Errors / metabolism*
  • Lipid Metabolism, Inborn Errors / pathology
  • Lysosomal Storage Diseases / genetics
  • Lysosomal Storage Diseases / metabolism*
  • Lysosomal Storage Diseases / pathology
  • Lysosomes / metabolism*
  • Lysosomes / pathology
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Multiprotein Complexes
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1