title: Autophagosomes contribute to intracellular lipid distribution in enterocytes.
abstract: Enterocytes, the intestinal absorptive cells, have to deal with massive alimentary lipids upon food consumption. They orchestrate complex lipid-trafficking events that lead to the secretion of triglyceride-rich lipoproteins and/or the intracellular transient storage of lipids as lipid droplets (LDs). LDs originate from the endoplasmic reticulum (ER) membrane and are mainly composed of a triglyceride (TG) and cholesterol-ester core surrounded by a phospholipid and cholesterol monolayer and specific coat proteins. The pivotal role of LDs in cellular lipid homeostasis is clearly established, but processes regulating LD dynamics in enterocytes are poorly understood. Here we show that delivery of alimentary lipid micelles to polarized human enterocytes induces an immediate autophagic response, accompanied by phosphatidylinositol-3-phosphate appearance at the ER membrane. We observe a specific and rapid capture of newly synthesized LD at the ER membrane by nascent autophagosomal structures. By combining pharmacological and genetic approaches, we demonstrate that autophagy is a key player in TG targeting to lysosomes. Our results highlight the yet-unraveled role of autophagy in the regulation of TG distribution, trafficking, and turnover in human enterocytes.
authors.affiliation: Centre de Recherche des Cordeliers, UMR S 872, Université Pierre et Marie Curie-Paris 6, Institut National de la Santé et de la Recherche Médicale, U 872 and UMR S 872, Université Paris Descartes-Paris 5, F-75006 Paris, France Laboratoire de Pharmacologie Cellulaire et Moléculaire, Ecole Pratique des Hautes Etudes, F-75006 Paris, France.
authors.forename: Salem Ait
authors.initials: SA
authors.lastname: Khaldoun
authors.forename: Marc-Alexandre
authors.initials: MA
authors.lastname: Emond-Boisjoly
authors.forename: Danielle
authors.initials: D
authors.lastname: Chateau
authors.forename: Véronique
authors.initials: V
authors.lastname: Carrière
authors.forename: Michel
authors.initials: M
authors.lastname: Lacasa
authors.forename: Monique
authors.initials: M
authors.lastname: Rousset
authors.forename: Sylvie
authors.initials: S
authors.lastname: Demignot
authors.forename: Etienne
authors.initials: E
authors.lastname: Morel
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001343:Autophagy; D001692:Biological Transport; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010588:Phagosomes / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate