2026-05-22T17:23:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/160622024-11-29T17:24:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Meçe, Odeta author Houbaert, Diede author Sassano, Maria-Livia author Durré, Tania author Maes, Hannelore author Schaaf, Marco author More, Sanket author Ganne, Maarten author García-Caballero, Melissa author Borri, Mila author Verhoeven, Jelle author Agrawal, Madhur author Jacobs, Kathryn author Bergers, Gabriele author Blacher, Silvia author Ghesquière, Bart author Dewerchin, Mieke author Swinnen, Johan V author Vinckier, Stefan author Soengas, MS author Carmeliet, Peter author Noël, Agnès author Agostinis, Patrizia author 2022-05-19 Autophagy has vasculoprotective roles, but whether and how it regulates lymphatic endothelial cells (LEC) homeostasis and lymphangiogenesis is unknown. Here, we show that genetic deficiency of autophagy in LEC impairs responses to VEGF-C and injury-driven corneal lymphangiogenesis. Autophagy loss in LEC compromises the expression of main effectors of LEC identity, like VEGFR3, affects mitochondrial dynamics and causes an accumulation of lipid droplets (LDs) in vitro and in vivo. When lipophagy is impaired, mitochondrial ATP production, fatty acid oxidation, acetyl-CoA/CoA ratio and expression of lymphangiogenic PROX1 target genes are dwindled. Enforcing mitochondria fusion by silencing dynamin-related-protein 1 (DRP1) in autophagy-deficient LEC fails to restore LDs turnover and lymphatic gene expression, whereas supplementing the fatty acid precursor acetate rescues VEGFR3 levels and signaling, and lymphangiogenesis in LEC-Atg5-/- mice. Our findings reveal that lipophagy in LEC by supporting FAO, preserves a mitochondrial-PROX1 gene expression circuit that safeguards LEC responsiveness to lymphangiogenic mediators and lymphangiogenesis. Nat Commun . 2022 ;13(1):2760. 10.1038/s41467-022-30490-6 2041-1723 Nature communications 35589749 http://hdl.handle.net/20.500.12105/16062 Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis.