At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy

Trends Biochem Sci. 2014 Feb;39(2):61-71. doi: 10.1016/j.tibs.2013.12.001. Epub 2013 Dec 24.

Abstract

In the past decade, autophagy studies have largely focused on the early stage of autophagy: the molecular mechanisms leading to autophagosome formation. Recently, however, we have observed significant progress in understanding the role of lysosomes, the specific cellular organelle that degrades cellular components delivered via autophagy. The discoveries include connections between autophagy and lysosomal biogenesis, activation, reformation, and turnover, as well as the identification of an autophagosomal SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein in control of autophagosome-lysosome fusion. We illustrate these findings in the context of the underlying molecular mechanisms and the relevance to human health and disease.

Keywords: autophagosome; autophagy; lysosome; mechanistic target of rapamycin complex 1; neurodegenerative diseases; soluble N-ethylmaleimide-sensitive factor attachment protein receptor; transcription factor EB.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arabidopsis / genetics
  • Arabidopsis / metabolism
  • Autophagy / genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation
  • Humans
  • Lysosomes / metabolism*
  • Lysosomes / pathology
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Phagosomes / metabolism*
  • Phagosomes / pathology
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Multiprotein Complexes
  • SNARE Proteins
  • TFEB protein, human
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Extracellular Signal-Regulated MAP Kinases