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Science 332 (6036): 1429-1433

Copyright © 2011 by the American Association for the Advancement of Science

TFEB Links Autophagy to Lysosomal Biogenesis

Carmine Settembre,1,2,3 Chiara Di Malta,1 Vinicia Assunta Polito,1,2,3 Moises Garcia Arencibia,4 Francesco Vetrini,2 Serkan Erdin,2,3 Serpil Uckac Erdin,2,3 Tuong Huynh,2,3 Diego Medina,1 Pasqualina Colella,1 Marco Sardiello,2,3 David C. Rubinsztein,4 Andrea Ballabio1,2,3,5,*

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.

1 Telethon Institute of Genetics and Medicine (TIGEM), Via Pietro Castellino 111, 80131 Naples, Italy.
2 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
3 Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX 77030, USA.
4 Cambridge Institute for Medical Research, Wellcome Trust–Medical Research Council Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 0XY, UK.
5 Medical Genetics, Department of Pediatrics, Federico II University, Via Pansini 5, 80131 Naples, Italy.

* To whom correspondence should be addressed. E-mail: ballabio{at}tigem.it

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