title: TFEB links autophagy to lysosomal biogenesis.
abstract: 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.
authors: Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
authors: Carmine
authors: C
authors: Settembre
authors: Chiara
authors: C
authors: Di Malta
authors: Vinicia Assunta
authors: VA
authors: Polito
authors: Moises
authors: M
authors: Garcia Arencibia
authors: Francesco
authors: F
authors: Vetrini
authors: Serkan
authors: S
authors: Erdin
authors: Serpil Uckac
authors: SU
authors: Erdin
authors: Tuong
authors: T
authors: Huynh
authors: Diego
authors: D
authors: Medina
authors: Pasqualina
authors: P
authors: Colella
authors: Marco
authors: M
authors: Sardiello
authors: David C
authors: DC
authors: Rubinsztein
authors: Andrea
authors: A
authors: Ballabio
references: Bioinformatics. 2008 Dec 15;24(24):2857-64
references: 18940828
references: Genome Biol. 2007;8(11):R250
references: 18039369
references: Mol Cell. 2010 Oct 22;40(2):310-22
references: 20965424
references: Cell. 2008 Jan 11;132(1):27-42
references: 18191218
references: Nat Cell Biol. 2011 Feb;13(2):132-41
references: 21258367
references: Nature. 2010 Jul 1;466(7302):68-76
references: 20562859
references: Nature. 1998 Jan 15;391(6664):298-301
references: 9440696
references: Nat Rev Mol Cell Biol. 2005 Nov;6(11):827-37
references: 16227978
references: Cell Metab. 2007 Dec;6(6):472-83
references: 18054316
references: Cell Metab. 2007 Dec;6(6):458-71
references: 18054315
references: Mol Biol Cell. 2004 Mar;15(3):1101-11
references: 14699058
references: Nat Neurosci. 2010 Jul;13(7):805-11
references: 20581817
references: Cell. 2007 Jun 29;129(7):1415-26
references: 17570479
references: Cell. 2005 Jan 28;120(2):237-48
references: 15680329
references: Science. 2010 Jul 9;329(5988):229-32
references: 20522742
references: Annu Rev Genet. 2009;43:67-93
references: 19653858
references: Curr Opin Cell Biol. 2010 Apr;22(2):140-9
references: 20097051
references: Science. 2009 Jul 24;325(5939):473-7
references: 19556463
references: Science. 2010 Dec 3;330(6009):1344-8
references: 21127245
references: Mol Cell Proteomics. 2008 Sep;7(9):1598-608
references: 18463090
references: Nat Biotechnol. 2007 Mar;25(3):285-6
references: 17344875
references: Genes Dev. 2007 Nov 15;21(22):2861-73
references: 18006683
references: Science. 2011 Jan 28;331(6016):456-61
references: 21205641
references: Cell. 2010 Feb 5;140(3):313-26
references: 20144757
references: Genes Dev. 2008 Oct 1;22(19):2645-50
references: 18832069
references: Neuroreport. 2004 Nov 15;15(16):2443-5
references: 15538170
references: Nat Cell Biol. 2008 Feb;10(2):138-48
references: 18204439
references: Methods Enzymol. 2009;452:47-61
references: 19200875
references: Hum Mol Genet. 2008 Jan 1;17(1):119-29
references: 17913701