2026-08-29T14:17:33Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/160622024-11-29T17:24:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Research Foundation - Flanders
funder
Stichting tegen Kanker
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Flemish Government
2023-05-16T09:06:25Z
2023-05-16T09:06:25Z
2022-05-19
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
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.
eng
Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis.
journal article
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