Tyrosine phosphatese SHP2 regulates arachidonic acid (AA) metabolismo and mitochondria rearrangement.

DUARTE ALEJANDRA; PODEROSO CECILIA; COOKE MARIANA; ORLANDO ULISES; CORNEJO MACIEL FABIANA; SORIA GASTÓN; GOTTIFREDI VANESA; PODESTÁ ERNESTO J

Los Cocos. Córdoba. Argentina

Simposio; Sistam; 2010

Symposium in Signal Transduction and Molecular Medicine” (SISTAM2010)

A previous report from our laboratory showed a new mechanism that controls the level of intramitochondrial AA and its conversion to lipoxygenase products in steroidogenic and cancer cells. This mechanism involves the action of an acyl-CoA syntetase (ACSL4) a key enzyme in the regulation of the aggressive phenotype in cancer cells that is regulated via the activation of Tyrosine Phosphatases (PTPs). Using overexpression and suppression approaches, we demonstrate that SHP-2 is, at least, one of the PTPs that play an obligatory role in this regulation. We have also demonstrated that activation of the cAMP signal leads to a translocation of PKA and ERK to the mitochondria. However, there is no description of a mitochondrial target signal in PKA and ERK. We observed that hormone treatment of the cells results in a rearrangement of mitochondria and that SHP2 knock-down abolishes the movement of the mitochondria and the translocation of ERK. Moreover the rearrangement of the mitochondria produces the association of ACSL4 and the microsomal associated membrane with the mitochondria. Thus, it seems that SHP-2 may control the mitochondrial movement to allow for the rearrangement of crucial mitochondria proteins involved in the generation of a protein complex that regulate cellular function.