ISSN:
1573-675X
Keywords:
Bcl-2
;
carnitine
;
fatty acids
;
mitochondrial megachannel
;
permeability transition pore.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract 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 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1009694124241
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