Coordinating Autophagy and Lysosome Regulation

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Science  17 Jun 2011:
Vol. 332, Issue 6036, pp. 1357
DOI: 10.1126/science.332.6036.1357-b
CREDIT: SETTEMBRE ET AL.

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. (p. 1429, published online 26 May; 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.

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