RT Journal Article
SR Electronic
T1 A SNX1–SNX2–VAPB partnership regulates endosomal membrane rewiring in response to nutritional stress
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201652
DO 10.26508/lsa.202201652
VO 6
IS 3
A1 Juliane Da Graça
A1 Juliette Charles
A1 Morgane Djebar
A1 Karla Alvarez-Valadez
A1 Joëlle Botti
A1 Etienne Morel
YR 2023
UL https://www.life-science-alliance.org/content/6/3/e202201652.abstract
AB Nutrient deprivation (“starvation”) is a major catabolic stress faced by mammalian cells in both pathological and physiological situations. Starvation induces autophagosome biogenesis in the immediate vicinity of ER and leads to lysosome spatial repositioning, but little is known about the consequences of nutritional stress on endosomes. Here, we report that starvation induces tethering of endosomal tubules to ER subregions, fostering autophagosome assembly. We show that this endosomal membrane generation is regulated by sorting nexin 1 (SNX1) protein and is important for the autophagic response. These newly formed SNX1 endosomal tubules establish connections with ER subdomains engaged in early autophagic machinery mobilization. Such endosome-ER transient tethers are regulated by a local dialog between SNX2, an endosomal partner of SNX1, and VAPB, an ER protein associated with autophagy initiation stage regulation. We propose that in a very early response to starvation, SNX1 and SNX2 cooperation induces and regulates endosomal membrane tubulation towards VAPB-positive ER subdomains involved in autophagosome biogenesis, highlighting the contribution of early endosomes in the cellular response to nutritional stress.