Termination of autophagy and reformation of lysosomes regulated by mTOR

Li Yu, Christina K. McPhee, Lixin Zheng, Gonzalo A. Mardones, Yueguang Rong, Junya Peng, Na Mi, Ying Zhao, Zhihua Liu, Fengyi Wan, Dale W. Hailey, Viola Oorschot, Judith Klumperman, Eric H. Baehrecke, Michael J. Lenardo

Research output: Contribution to journalArticle

Abstract

Autophagy is an evolutionarily conserved process by which cytoplasmic proteins and organelles are catabolized. During starvation, the protein TOR (target of rapamycin), a nutrient-responsive kinase, is inhibited, and this induces autophagy. In autophagy, double-membrane autophagosomes envelop and sequester intracellular components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients. Current models of autophagy terminate with the degradation of the autophagosome cargo in autolysosomes, but the regulation of autophagy in response to nutrients and the subsequent fate of the autolysosome are poorly understood. Here we show that mTOR signalling in rat kidney cells is inhibited during initiation of autophagy, but reactivated by prolonged starvation. Reactivation of mTOR is autophagy-dependent and requires the degradation of autolysosomal products. Increased mTOR activity attenuates autophagy and generates proto-lysosomal tubules and vesicles that extrude from autolysosomes and ultimately mature into functional lysosomes, thereby restoring the full complement of lysosomes in the cella process we identify in multiple animal species. Thus, an evolutionarily conserved cycle in autophagy governs nutrient sensing and lysosome homeostasis during starvation.

Original languageEnglish (US)
Pages (from-to)942-946
Number of pages5
JournalNature
Volume465
Issue number7300
DOIs
StatePublished - Jun 17 2010
Externally publishedYes

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Autophagy
Lysosomes
Starvation
Food
TOR Serine-Threonine Kinases
Organelles
Homeostasis
Phosphotransferases
Kidney
Membranes

ASJC Scopus subject areas

  • General

Cite this

Yu, L., McPhee, C. K., Zheng, L., Mardones, G. A., Rong, Y., Peng, J., ... Lenardo, M. J. (2010). Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature, 465(7300), 942-946. https://doi.org/10.1038/nature09076

Termination of autophagy and reformation of lysosomes regulated by mTOR. / Yu, Li; McPhee, Christina K.; Zheng, Lixin; Mardones, Gonzalo A.; Rong, Yueguang; Peng, Junya; Mi, Na; Zhao, Ying; Liu, Zhihua; Wan, Fengyi; Hailey, Dale W.; Oorschot, Viola; Klumperman, Judith; Baehrecke, Eric H.; Lenardo, Michael J.

In: Nature, Vol. 465, No. 7300, 17.06.2010, p. 942-946.

Research output: Contribution to journalArticle

Yu, L, McPhee, CK, Zheng, L, Mardones, GA, Rong, Y, Peng, J, Mi, N, Zhao, Y, Liu, Z, Wan, F, Hailey, DW, Oorschot, V, Klumperman, J, Baehrecke, EH & Lenardo, MJ 2010, 'Termination of autophagy and reformation of lysosomes regulated by mTOR', Nature, vol. 465, no. 7300, pp. 942-946. https://doi.org/10.1038/nature09076
Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature. 2010 Jun 17;465(7300):942-946. https://doi.org/10.1038/nature09076
Yu, Li ; McPhee, Christina K. ; Zheng, Lixin ; Mardones, Gonzalo A. ; Rong, Yueguang ; Peng, Junya ; Mi, Na ; Zhao, Ying ; Liu, Zhihua ; Wan, Fengyi ; Hailey, Dale W. ; Oorschot, Viola ; Klumperman, Judith ; Baehrecke, Eric H. ; Lenardo, Michael J. / Termination of autophagy and reformation of lysosomes regulated by mTOR. In: Nature. 2010 ; Vol. 465, No. 7300. pp. 942-946.
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