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

Han-Ming Shen; Noboru Mizushima

doi:10.1016/j.tibs.2013.12.001

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.

Authors

Han-Ming Shen¹, Noboru Mizushima²

Affiliations

¹ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: han-ming_shen@nuhs.edu.sg.
² Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: nmizu@m.u-tokyo.ac.jp.

PMID: 24369758
DOI: 10.1016/j.tibs.2013.12.001

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
Mechanistic Target of Rapamycin Complex 1
TOR Serine-Threonine Kinases
Extracellular Signal-Regulated MAP Kinases