TY - JOUR
T1 - TFEB links autophagy to lysosomal biogenesis
AU - Settembre, Carmine
AU - Di Malta, Chiara
AU - Polito, Vinicia Assunta
AU - Arencibia, Moises Garcia
AU - Vetrini, Francesco
AU - Erdin, Serkan
AU - Erdin, Serpil Uckac
AU - Huynh, Tuong
AU - Medina, Diego
AU - Colella, Pasqualina
AU - Sardiello, Marco
AU - Rubinsztein, David C.
AU - Ballabio, Andrea
PY - 2011/6/17
Y1 - 2011/6/17
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=80955177196&partnerID=8YFLogxK
U2 - 10.1126/science.1204592
DO - 10.1126/science.1204592
M3 - Article
C2 - 21617040
AN - SCOPUS:80955177196
VL - 332
SP - 1429
EP - 1433
JO - Science
JF - Science
SN - 0036-8075
IS - 6036
ER -