ANGIOTENSIN II PROMOTES THE SUBCELLULAR DISTRIBUTION OF MTORC PATHWAY PROTEINS IN H295R HUMAN ADRENAL CELLS

ARGENTINO, GIULIANA; FINOCCHIETTO, PAOLA; HERRERA, LUCÍA; HELFENBERGER, KATIA E.; PODEROSO, CECILIA

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Target of rapamycin (TOR) forms two kinase complexes named mTOR complex 1 and 2 (mTORC1/2). mTORC1 regulates cellular growth by phosphorylation of a different set of components, such as p70 S6 kinase and S6 ribosomal protein (S6), among others, which promotes protein synthesis by cap-dependent translation through the eukaryotic initiation factor 4E. Canonical PI3K/Akt pathway activates mTORC1 and Akt is able to activate mTORC2. Glycogen-synthase kinase-3 (GSK-3) pathway negatively regulates mTORC1 by phosphorylation and activation of an mTOR inhibitory protein. We have previously shown that mTORC1/2 are activated in human adrenal cells by angiotensin II (Ang II) with the involvement of a key steroidogenic enzyme, acyl-CoA synthetase 4. Proteins subcellular localization is a general principle used by hormones and growth factors to endorse precise spatial and temporal control of cellular functions. mTORC1/2 are localized in distinct subcellular compartments suggested to be an important mechanism to achieve signaling specificity. Thus, the aim of this work was to analyze the subcellular distribution of some components of mTORC1/2 pathway under Ang II stimulation in H295R human adrenal cells. We performed subcellular fractionation and observed by immunoblot that Ang II promotes mitochondrial Akt phosphorylation (pAkt) in a time-dependent manner (control vs. Ang II; ***p