ANALYSIS OF THE REGULATORY MECHANISMS OF MITOFUSIN 2 GENE EXPRESSION IN H295R HUMAN ADRENAL CELLS

HELFENBERGER, KATIA E.; ARGENTINO, GIULIANA; BENZO, YANINA; PODEROSO, CECILIA; DATTILO, MELINA A.; MALOBERTI, PAULA M.

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Mitofusin 2 (Mfn2) is one of the most relevant mitochondrial proteins controlling mitochondrial fusion. Mfn2 accurate expression is involved in mitophagy, apoptosis, mitochondrial metabolism in mammalian cells and it is down regulated in obesity and in type 2 diabetic patients and mutated in Charcot-Marie-Tooth type 2A neuropathy. We have previously shown that angiotensin II (Ang II) promotes Mfn2 mRNA and protein expression and that Mfn2 is necessary for steroid synthesis in H295R human adrenal cells. It has been described that Mfn2 gene expression regulation involves several transcription factors, such as Sp1 and estrogen-related receptor-alpha (ERRalpha). We have observed that ERRalpha up-regulates Mfn2 expression in H295R cells. Then the aim of this study was to analyze the mechanisms involved in the regulation of basal and hormone-stimulated Mfn2 gene expression, and a possible role of ERRalpha in adrenal human cells. For this purpose, two reporter constructs were generated: a full length Mfn2 promoter including exon 1 (large) and a Mfn2 promoter with a deletion of the 5? end from position ?2700 to ?700 pb (short), both constructions containing ERRalpha binding sites. We observed that both promoters display activity in H295R human adrenal cells as detected by luciferase assay, but the short promoter presents three times more activity than the large one (***p