Abstract:
:Organs and cells must adapt to shear stress induced by biological fluids, but how fluid flow contributes to the execution of specific cell programs is poorly understood. Here we show that shear stress favours mitochondrial biogenesis and metabolic reprogramming to ensure energy production and cellular adaptation in kidney epithelial cells. Shear stress stimulates lipophagy, contributing to the production of fatty acids that provide mitochondrial substrates to generate ATP through β-oxidation. This flow-induced process is dependent on the primary cilia located on the apical side of epithelial cells. The interplay between fluid flow and lipid metabolism was confirmed in vivo using a unilateral ureteral obstruction mouse model. Finally, primary cilium-dependent lipophagy and mitochondrial biogenesis are required to support energy-consuming cellular processes such as glucose reabsorption, gluconeogenesis and cytoskeletal remodelling. Our findings demonstrate how primary cilia and autophagy are involved in the translation of mechanical forces into metabolic adaptation.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Miceli C,Roccio F,Penalva-Mousset L,Burtin M,Leroy C,Nemazanyy I,Kuperwasser N,Pontoglio M,Friedlander G,Morel E,Terzi F,Codogno P,Dupont Ndoi
10.1038/s41556-020-0566-0subject
Has Abstractpub_date
2020-09-01 00:00:00pages
1091-1102issue
9eissn
1465-7392issn
1476-4679pii
10.1038/s41556-020-0566-0journal_volume
22pub_type
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