Effect of arachidonic acid on cholesterol transport in mitochondria

CASTILLO FERNANDA; CONVERSO DANIELA; DUARTE ALEJANDRA; PODEROSO J; PODESTÁ ERNESTO J

Pinamar, Buenos Aires, Argentina

Congreso; SAIB 41th Annual Meeting, SAN 20th Annual Meeting and PABMB 10th Congress. Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).; 2005

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).

We have previously described a novel pathway for arachidonic acid (AA) release that involves an AA-preferring acyl-CoA synthetase (ACS4) and an acyl-CoA thioesterase (Acot2). ACS4 sequesters free AA thus forming an intracellular pool of Arachidonoyl-CoA (AA-CoA) that is delivered to Acot2 that, in its turn, releases AA in a specific compartment of the cell, the mitochondria. AA increases the expression of Steroidogenic Acute Regulatory protein (StAR) and cholesterol transport. Since AA is released into the mitochondria, a direct effect of this fatty acid on cholesterol transport can not be excluded. In order to test this hypothesis, we studied the effect of AA on cholesterol transport, determined as progesterone (P4) production in isolated mitochondria from non-stimulated MA-10 steroidogenic cells. AA elicited a stimulatory effect on cholesterol transport (0.17±0.03 vs. 0.09±0.02 ng P4/mg protein). This effect was not affected by the addition of cycloheximide, a protein synthesis inhibitor, indicating that it is independent of StAR protein induction. AA-CoA, the substrate of Acot2, increased also cholesterol transport in isolated mitochondria (0.23±0.04 vs. 0.09±0.02 ng P4/ mg protein). Our results indicate that AA per se stimulates cholesterol transport in mitochondria. This may be mediated by increasing membrane fluidity at the outer/inner mitochondrial membrane contact sites that facilitate the cholesterol transfer into the mitochondria.