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

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

Congreso; LXIV Reunión anual de la sociedad argentina de investigaciones clínicas; 2019

Mitofusin 2 (Mfn2) is one of the mostrelevant mitochondrial proteins controlling mitochondrial fusion.Mfn2 accurate expression is involved in mitophagy, apoptosis,mitochondrial metabolism in mammalian cells and it is downregulated in obesity and in type 2 diabetic patients and mutatedin Charcot-Marie-Tooth type 2A neuropathy. We have previouslyshown that angiotensin II (Ang II) promotes Mfn2 mRNA andprotein expression and that Mfn2 is necessary for steroidsynthesis in H295R human adrenal cells. It has been describedthat Mfn2 gene expression regulation involves severaltranscription factors, such as Sp1 and estrogen-related receptoralpha (ERRalpha). We have observed that ERRalpha up-regulatesMfn2 expression in H295R cells. Then the aim of this study wasto analyze the mechanisms involved in the regulation of basaland hormone-stimulated Mfn2 gene expression, and a possiblerole of ERRalpha in adrenal human cells. For this purpose, tworeporter constructs were generated: a full length Mfn2 promoterincluding exon 1 (large) and a Mfn2 promoter with a deletion ofthe 5? end from position ?2700 to ?700 pb (short), bothconstructions containing ERRalpha binding sites. We observedthat both promoters display activity in H295R human adrenalcells as detected by luciferase assay, but the short promoterpresents three times more activity than the large one(***p