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TFEB Links Autophagy to Lysosomal Biogenesis

2011; American Association for the Advancement of Science; Volume: 332; Issue: 6036 Linguagem: Inglês

10.1126/science.1204592

1095-9203

Carmine Settembre, Chiara Di Malta, Vinicia Assunta Polito, Moisés Garcı́a-Arencibia, Francesco Vetrini, Serkan Erdin, Serpil Uckac Erdin, Tuong Huynh, Diego L. Medina, Pasqualina Colella, Marco Sardiello, David C. Rubinsztein, Andrea Ballabio,

Lysosomal Storage Disorders Research

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.