title: The NOTCH1-autophagy interaction: Regulating self-eating for survival.
abstract: T-cell subsets in the mammalian immune system use varied mechanisms for survival, a demand imposed by the diverse and dynamic niches that they function in. In a recent study, we showed that survival of natural T-regulatory cells (Tregs) was determined by spatially regulated NOTCH1 activity signaling leading to the activation of macroautophagy/autophagy. While this interaction was revealed in experimental conditions of limited nutrient availability in vitro, the consequences of this interaction were confirmed in the context of immune physiology. Consistently, disrupting NOTCH signaling or the autophagy cascade was deleterious to Tregs. At the molecular level, ligand-activated NOTCH1, which is enriched outside the nucleus in Tregs, was detected in complexes that included specific molecular intermediates controlling the progression of autophagy. Mitochondria were a prominent cellular target, with organelle remodeling and function dependent on NOTCH1 signaling to autophagy. It is tempting to speculate that the link between autophagy and the developmental regulator NOTCH1 identified in this work may be conserved in other biological contexts.
authors.affiliation: a Institute for Stem Cell Biology & Regenerative Medicine , Bengaluru , Karnataka , India.
authors.forename: Apurva
authors.initials: A
authors.lastname: Sarin
authors.affiliation: a Institute for Stem Cell Biology & Regenerative Medicine , Bengaluru , Karnataka , India.
authors.forename: Nimi
authors.initials: N
authors.lastname: Marcel
mesh_terms: D000818:Animals; D001343:Autophagy; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D006801:Humans; D008954:Models, Biological; D051881:Receptor, Notch1 / Q000378:metabolism*
chemical_list: D051881:Receptor, Notch1
keywords: NOTCH1; T-regulatory cells; autophagy; mitochondrial; survival