title: Palmitate induces apoptosis via a direct effect on mitochondria.
abstract: The fatty acid palmitate can induce apoptosis. Here we show that the palmitate-induced dissipation of the mitochondrial transmembrane potential (Delta Psi m), which precedes nuclear apoptosis, is not prevented by inhibitors of mRNA synthesis, protein synthesis, caspases, or pro-apoptotic ceramide signaling. However, the mitochondrial and nuclear effects of palmitate are inhibited by overexpression of anti-apoptotic proto-oncogene product Bcl-2 and exacerbated by 2-bromo-palmitate as well as by carnitine. The cytoprotective actions of Bcl-2, respectively, is not antagonized by etomoxir, an inhibitor of carnitine palmitoyl transferase 1 (CPT1), suggesting that the recently described physical interaction between CPT1 and Bcl-2 is irrelevant to Bcl-2-mediated inhibition of palmitate-induce apoptosis. When added to purified mitochondria, palmitate causes the release of soluble factors capable of stimulating the apoptosis of isolated nuclei in a cell-free system. Mitochondria purified from Bcl-2 over-expressing cells are protected against the palmitate-stimulated release of such factors. These data suggest that palmitate causes apoptosis via a direct effect on mitochondria.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Propre de Recherche 420, 19 rue Guy Môquet, F-94801 Villejuif, France.
authors.forename: M A
authors.initials: MA
authors.lastname: de Pablo
authors.forename: S A
authors.initials: SA
authors.lastname: Susin
authors.forename: E
authors.initials: E
authors.lastname: Jacotot
authors.forename: N
authors.initials: N
authors.lastname: Larochette
authors.forename: P
authors.initials: P
authors.lastname: Costantini
authors.forename: L
authors.initials: L
authors.lastname: Ravagnan
authors.forename: N
authors.initials: N
authors.lastname: Zamzami
authors.forename: G
authors.initials: G
authors.lastname: Kroemer