MITOCHONDRIAL ATP SYNTHESIS AND ITS ROLE IN ARACHIDONIC ACID RELEASE AND METABOLISM IN THIS ORGANELLE

DUARTE, ALEJANDRA; CASTILLO, FERNANDA; CASTILLA, ROCÍO; MALOBERTI, PAULA; PAZ, CRISTINA; PODESTÁ, ERNESTO J.; CORNEJO MACIEL, FABIANA

. Rosario, Santa Fe, Argentina

Congreso; XLII Annual Meeting of Argentine Society for Biochemistry and Molecular Biology (SAIB); 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

It has been shown that prevention of electron transport in mitochondria with antimycin A (ActA) and inhibition of mitochondrial ATP synthesis with oligomycin (Oly) significantly reduces cellular ATP, potently inhibits cholesterol transport, and reduces a protein involved in cholesterol transport (StAR). Since cholesterol transport and the expression of the StAR are dependent of Arachidonic Acid (AA) release in a specific compartment of the cells (the mitochondria), the purpose of this work was to study the effect of ActA and Oly on AA release and metabolism induced by cAMP in steroidogenic cells. MA-10 Leydig cells were incubated with cAMP (1 mM) alone or in combination with AA, in the presence or absence of ActA and Oly (1 uM). After 3 hours cholesterol transport, AA release and StAR induction were determined. ActA and Oly significantly reduced cholesterol transport and StAR induction induced by cAMP. AA was able to overcome this inhibition. ActA and Oly produced an increase in the accumulation of AA release into the mitochondria. Since the induction of cholesterol transport and StAR protein are dependent on AA release and metabolism to lipoxygenated products, these results suggest that disrupting ATP content abolishes the access of AA to lipoxygenase enzyme with the consequent inhibition of cholesterol transport and StAR induction in mitochondria.