Estrogen- related receptor alpha is involved in the regulation of mitofusin 2 expression in adrenocortical human cells

HELFENBERGER KATIA; CASTILLO FERNANDA; BENZO YANINA; ARGENTINO GIULIANA; MALOBERTI PAULA; PODEROSO CECILIA

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Mitofusin 2 (Mfn2) is a mitochondrial protein that participates in mitochondrial fusion, protects against apoptosis and activates mitochondrial metabolism in mammalian cells. Mfn2 expression is downregulated in obesity and in type 2 diabetic patients and mutations in this protein cause neurodegenerative diseases, like Charcot-Marie-Tooth type 2A neuropathy. It has been described that Mfn2 gene expression regulation involves several transcription factors. Mfn2 can be induced directly by the cooperative action of PPAR-γ coactivator-1α (PGC-1α) and estrogen-related receptor-α (ERRα). We have previously shown in adrenocortical human cells that Angiotensin II (Ang II) regulates Mfn2 expression by increasing its mRNA and concomitantly its mitochondrial localization. The aim of this work was to study the role of ERRα on the regulation of Mfn2 expression in adrenal cells. We observed in H295R adrenocortical human cells that stimulation with Ang II modulates ERRα protein in a time-dependent manner. Then, we demonstrated by qPCR that ERRα overexpression increases Mfn2 mRNA in control and in Ang II-stimulated cells (Mock vs. ERRα: 1 vs. 4.51, Mock + Ang II vs ERRα + Ang II: 5.46 vs. 8.77 ***p