TFEB Links Autophagy to Lysosomal Biogenesis

By C. Settembre, Chiara Di Malta, V. A. Polito, Moises Garcia Arencibia, F. Vetrini, Serkan Erdin, S. Erdin, Tuong Huynh, Diego L. Medina, P. Colella and 3 more. Science, 2011

3,107 citations recorded by the source corpus.

Starvation activates a transcriptional program controlling autophagosome formation, lysosome fusion, and substrate degradation. 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.

Subfields: Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/75bc6d47a729b2066a62899cc8a0c04e4e8c70c3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

In Physiology

Citations in the corpus

mTOR: a pharmacologic target for autophagy regulation. (2015, neutral): “The transcriptional activity of TFEB is regulated by nutrient and phosphorylation-dependent cyto-plasm-to-nucleus shuttling (75).”
Guidelines for the use and interpretation of assays for monitoring autophagy (2012, background): “For example, this can be achieved either through overexpression or post-translational activation of the gene encoding TFEB (see Transcriptional and translational regulation), a transcriptional regulator of the biogenesis of both lysosomes and autophagosomes.(463,464) Similarly, adenoviral-mediated e”
Lysosomal membrane permeabilization and cell death (2018, background): “This phenomenon is probably related to TFEB activation; lysosomal enlargement has been shown to induce activation of TFEB as a compensatory mechanism to generate more lysosomes.(16,35)”
TFEB-mediated autophagy rescues midbrain dopamine neurons from α-synuclein toxicity (2013, background): “Recently, Ballabio and colleagues identified the transcription factor EB (TFEB) as a master regulator of the ALP (35, 36), controlled by mTOR signaling (37–39).”
Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. (2011, background): “autophagosomes, the fusion between lysosomes and autophagosomes and the autophagic flux, thus representing a link between autophagy and lysosomal biogenesis (18).”
Astrocytes: a central element in neurological diseases (2016, neutral): “proteins [199, 200, 257]; and remove abnormal aggregates”
mTOR signaling in growth control and disease (2012, positive): “Interestingly, because TFEB controls the expression of several genes that promote autophagosome formation and fusion to lysosomes, it is likely that the mTORC1/TFEB connection also plays a significant role in promoting autophagy when nutrient levels are low (Settembre et al., 2011).”
TFEB at a glance (2016, background): “Accordingly, variants of TFEB carrying Ser-to-Ala mutations of either Ser142 or Ser211 are always nuclear and constitutively active (Martina et al., 2012; Roczniak-Ferguson et al., 2012; Settembre et al., 2011, 2012).”
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2012, neutral): “some and autophagosome biogenesis was identified using a systems-biology approach.(625,635,636) The basic helix-loophelix transcription factor TFEB acts as a master gene of the”
Autophagy and apoptosis dysfunction in neurodegenerative disorders. (2014, positive): “Autophagy induction is frequently associated by up-regulated hydrolase synthesis and increased lysosome biogenesis (Settembre et al., 2011).”