Publication Date:
2011-05-28
Description:
Autophagy is a cellular catabolic process that relies on the cooperation of autophagosomes and lysosomes. During starvation, the cell expands both compartments to enhance degradation processes. We found that starvation activates a transcriptional program that controls major steps of the autophagic pathway, including autophagosome formation, autophagosome-lysosome fusion, and substrate degradation. The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. Nuclear localization and activity of TFEB were regulated by serine phosphorylation mediated by the extracellular signal-regulated kinase 2, whose activity was tuned by the levels of extracellular nutrients. Thus, a mitogen-activated protein kinase-dependent mechanism regulates autophagy by controlling the biogenesis and partnership of two distinct cellular organelles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638014/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3638014/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Settembre, Carmine -- Di Malta, Chiara -- Polito, Vinicia Assunta -- Garcia Arencibia, Moises -- Vetrini, Francesco -- Erdin, Serkan -- Erdin, Serpil Uckac -- Huynh, Tuong -- Medina, Diego -- Colella, Pasqualina -- Sardiello, Marco -- Rubinsztein, David C -- Ballabio, Andrea -- 250154/European Research Council/International -- 5 P30 HD024064/HD/NICHD NIH HHS/ -- G0600194/Medical Research Council/United Kingdom -- P30 HD024064/HD/NICHD NIH HHS/ -- R01 NS078072/NS/NINDS NIH HHS/ -- TGM11CB6/Telethon/Italy -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Jun 17;332(6036):1429-33. doi: 10.1126/science.1204592. Epub 2011 May 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21617040" target="_blank"〉PubMed〈/a〉
Keywords:
Active Transport, Cell Nucleus
;
Animals
;
*Autophagy
;
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/*metabolism
;
COS Cells
;
Cell Nucleus/*metabolism
;
Cells, Cultured
;
Cercopithecus aethiops
;
Cytoplasm/metabolism
;
Gene Expression Regulation
;
HeLa Cells
;
Humans
;
Liver/metabolism
;
Lysosomes/*metabolism
;
MAP Kinase Signaling System
;
Mice
;
Mice, Transgenic
;
Microtubule-Associated Proteins/metabolism
;
Mitogen-Activated Protein Kinase 1/metabolism
;
Phagosomes/metabolism
;
Phosphorylation
;
RNA Interference
;
Transcription, Genetic
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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