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

• Published in: Trends in biochemical sciences (Amsterdam. Regular ed.) Vol. 39; no. 2; pp. 61 - 71
• Main Authors: Shen, Han-Ming, Mizushima, Noboru
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2014
• Subjects: Animals; Arabidopsis - genetics; Arabidopsis - metabolism; autophagosome; autophagy; Autophagy - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; biogenesis; Extracellular Signal-Regulated MAP Kinases - genetics; Extracellular Signal-Regulated MAP Kinases - metabolism; Gene Expression Regulation; human health; Humans; lysosome; lysosomes; Lysosomes - metabolism; Lysosomes - pathology; Mechanistic Target of Rapamycin Complex 1; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; neurodegenerative diseases; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - pathology; Phagosomes - metabolism; Phagosomes - pathology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Signal Transduction; SNARE proteins; SNARE Proteins - genetics; SNARE Proteins - metabolism; soluble N-ethylmaleimide-sensitive factor attachment protein receptor; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; transcription factor EB; soluble N-ethylmaleimide-sensitive factor attachment protein receptor; neurodegenerative diseases; autophagy; mechanistic target of rapamycin complex 1; transcription factor EB; lysosome; autophagosome
• ISSN: 0968-0004; 1362-4326
• DOI: 10.1016/j.tibs.2013.12.001

•Lysosomes perform the key degradative function for all forms of autophagy.•TFEB-mediated lysosomal biogenesis occurs via suppression of MTORC1.•Lysosomes are consumed and reformed by autophagy.•Stx17 is a newly-discovered autophagosomal SNARE that mediates autophagosome–lysosome fusion.•Lysosomal function is activated via MTORC1 inhibition and autophagosome fusion. 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.