Intramitochondrial arachidonic acid as regulator of two different cellular functions: steroid biosynthesis and tumor cell proliferation

CASTILLO, ANA FERNANADA; CASTILLA, ROCÍO; DUARTE, ALEJANDRA; MELE, PABLO; ORLANDO, ULISES; KARLES, CRISTINA; NEUMAN, ISABEL; DI CÓNSOLI, HERNÁN; PODEROSO, CECILIA; SOLANO, ANGELA; FINKIELSTEIN, CARLA; MALOBERTI, PAULA; CORNEJO MACIEL, FABIANA; PAZ, CRISTINA; PODESTÁ, ERNESTO J.

Current Trends in Endocrinology

Reaserch Trends

Lugar: Kerala, India; Año: 2008 vol. 3 p. 57 - 75

0972-947X

Long-chain fatty acids represent a major energy source for many organs. However besides this basal function, long-chain-acyl-CoA esters also have an important function in cell signaling. Arachidonic acid (AA) is a 20-carbon fatty acid and it is a common constituent of phospholipids in cell membranes. On stimulation of a cell, free AA is released and it may be metabolized via the cyclooxygenase, lipoxygenase or epoxygenase pathways. How the cells drive AA to these pathways is not fully described. Several reports have shown that AA and its lipoxygenated and epoxygenated products play an essential role in the regulation of steroidogenesis, acting at a point between cAMP-dependent protein phosphorylation and the rate limiting step of the biosynthetic pathway i.e., the metabolism of cholesterol to pregnenolone, which is in turn limited by the transport of cholesterol from the outer to the inner mitochondrial membrane. Cholesterol transfer is controlled by a multiple protein complex including the translocator protein and the steroidogenic acute regulatory protein (StAR). This topic has been well  covered in specialized reviews. However, how different protein hormones regulate this universal process in steroid biosynthesis throughout different signal transduction mechanisms in different tissues is still not cover by any review. AA is one of the common intermediates in the regulation of steroid biosynthesis by different factors. This review covers the mechanism by which steroidogenic hormones control AA release and metabolization to lipoxy-genated and epoxygenated metabolites to induce StAR protein and steroidogenesis and how AA is related also to proliferation and carcinogenesis.