Editors' ChoiceAUTOPHAGY

Coordinating Autophagy and Lysosome Regulation

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Sci. Signal.  21 Jun 2011:
Vol. 4, Issue 178, pp. ec175
DOI: 10.1126/scisignal.4178ec175

Autophagy involves the degradation of intracellular proteins and organelles and is often promoted as a response to starvation that allows for the reuse of constituent amino acids. How do cells coordinate protein degradation and recycling processes? Settembre et al. (see the Perspective by Cuervo) identified a biological mechanism that regulates, in a coordinated fashion, the function of two cellular organelles, autophagosomes and lysosomes, whose synergy is required for an efficient autophagic process. During starvation, cells activated a transcriptional program that controls all 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 both autophagy and lysosomal genes. Furthermore, TFEB activity was regulated by the mitogen-activated protein (MAP) kinase ERK2, which implicates the kinase signaling pathway in the control of autophagy.

C. Settembre, C. Di Malta, V. Assunta Polito, M. Garcia Arencibia, F. Vetrini, S. Erdin, S. Uckac Erdin, T. Huynh, D. Medina, P. Colella, M. Sardiello, D. C. Rubinsztein, A. Ballabio, TFEB links autophagy to lysosomal biogenesis. Science 332, 1429–1433 (2011). [Abstract] [Full Text]

A. M. Cuervo, Autophagy’s top chef. Science 332, 1392–1393 (2011). [Abstract] [Full Text]