Phosphorylation of Acyl-CoA synthetase 4 (ACSL4) in steroidogenic cells

CASTILLA, ROCÍO; SMITH, EMILIA; PODESTÁ, ERNESTO J.

Los Cocos, Córdoba

Simposio; The First South American Spring Symposium in Signal Tranduction and Molecular Medicine; 2010

Acsl4, an arachidonic acid (AA) preferring enzyme, is key in the regulation of AA intracellular levels and steroidogenesis. Acsl4 is a protein with a high turn over rate, located in mitochondria-associated membranes (MAM) that acts in a dimer form. Steroid synthesis is regulated by different hormones or factors through PKA and/or PKC-mediated protein phosphorylation. Sequence analysis of Acsl4 shows the presence of PKA and PKC consensus sites. Thus, the aim of this study was to determine whether Acsl4 is substrate of these kinases. We demonstrated that recombinant Acsl4 is independently phosphorylated in vitro by PKA and PKC kinases. We also demonstrated that Acsl4 is phosphorylated by adrenocorticotrophin hormone in Y1 adrenal cells. The phosphorylation of Acsl4 does not regulate dimer formation but it increases the activity of the enzyme. Protein phosphorylation is essential for MAM/mitochondria association. Since Acsl4 participate in this association, Acsl4 phosphorylation may play a role in this mechanism.