Tyrosine phosphatase SHP2 regulates arachidonic acid (AA) metabolism and mitochondria rearrangement

DUARTE, A; PODEROSO, C; COOKE, M; ORLANDO, U; CORNEJO MACIEL, F; SORIA, G; GOTTIFREDI, V, PODESTA, EJ

Los Cocos, Cordoba

Congreso; The First South American Spring Symposium in Signal Transduction and Molecular Medicine” (SISTAM2010); 2010

A previous report from our laboratory showed a new mechanism that controls the level ofintramitochondrial AA and its conversion to lipoxygenase products in steroidogenic andcancer cells. This mechanism involves the action of an acyl-CoA syntetase (ACSL4) a keyenzyme in the regulation of the aggressive phenotype in cancer cells that is regulated viathe activation of Tyrosine Phosphatases (PTPs).Using overexpression and suppressionapproaches, we demonstrate that SHP-2 is, at least, one of the PTPs that play anobligatory role in this regulation. We have also demonstrated that activation of the cAMPsignal leads to a translocation of PKA and ERK to the mitochondria. However, there is nodescription of a mitochondrial target signal in PKA and ERK. We observed that hormonetreatment of the cells results in a rearrangement of mitochondria and that SHP2 knockdownabolishes the movement of the mitochondria and the translocation of ERK. Moreoverthe rearrangement of the mitochondria produces the association of ACSL4 and themicrosomal associated membrane with the mitochondria. Thus, it seems that SHP-2 maycontrol the mitochondrial movement to allow for the rearrangement of crucial mitochondriaproteins involved in the generation of a protein complex that regulate cellular function.