Palmitate induces apoptosis via a direct effect on mitochondria

M. A. De Pablo, S. A. Susin, E. Jacotot, N. Larochette, P. Costantini, L. Ravagnan, N. Zamzami, G. Kroemer

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Résumé

The fatty acid palmitate can induce apoptosis. Here we show that the palmitate-induced dissipation of the mitochondrial transmembrane potential (ΔΨ(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 overexpressing cells are protected against the palmitate-stimulated release of such factors. These data suggest that palmitate causes apoptosis via a direct effect on mitochondria.

langue originaleAnglais
Pages (de - à)81-87
Nombre de pages7
journalApoptosis
Volume4
Numéro de publication2
Les DOIs
étatPublié - 1 janv. 1999
Modification externeOui

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