RT Journal Article
T1 Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis.
A1 Meçe, Odeta
A1 Houbaert, Diede
A1 Sassano, Maria-Livia
A1 Durré, Tania
A1 Maes, Hannelore
A1 Schaaf, Marco
A1 More, Sanket
A1 Ganne, Maarten
A1 García-Caballero, Melissa
A1 Born, Mila
A1 Verhoeven, Jelle
A1 Agrawal, Madhur
A1 Jacobs, Kathryn
A1 Bergers, Gabriele
A1 Blacher, Silvia
A1 Ghesquière, Bart
A1 Dewerchin, Mieke
A1 Swinnen, Johan V.
A1 Vinckier, Stefan
A1 Soengas, María S.
A1 Carmeliet, Peter
A1 Noël, Agnès
A1 Agostinis, Patrizia
K1 Células - Metabolismo
AB 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.
PB SpringerNature
YR 2022
FD 2022-05-19
LK https://hdl.handle.net/10630/27105
UL https://hdl.handle.net/10630/27105
LA eng
NO Meçe, O., Houbaert, D., Sassano, ML. et al. Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis. Nat Commun 13, 2760 (2022). https://doi.org/10.1038/s41467-022-30490-6
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026