Alterations in NHE1 overexpressing mitochondria

RAYEN DE FAZIO; CIANCIO MC; ORLOWSKI A; AIELLO EA.; JAQUENOD DE GUISTI C

La Plata

Congreso; Congreso ISHR LATIN AMERICA; 2022

Alterations in NHE1 overexpressing mitochondriaRayen De Fazio, María C. Ciancio, Alejandro Orlowski, Ernesto A. Aiello, Carolina Jaquenod De GiustiCentro de Investigaciones Cardiovasculares – CONICET – UNLP – Facultad de Ciencias MédicasMitochondria are not only implicated in energy production but also in pathological events. Mitochondrial dysfunction has been related to the development of several pathologies including heart failure and diabetes. The Na+/H+ exchanger 1 (NHE1) is one of the main alkalinizing mechanisms in the heart and its hyperactivity has been observed in several heart conditions, including diabetic cardiomyopathy. In obese and diabetic mice mitochondria NHE1 expression is increased despite similar cardiac levels, together with altered calcium handling reverted in the presence of an NHE1 inhibitor.Aim: understanding the consequences of increased mitochondrial NHE1 expression.Materials and methods: HEK293T cells were transfected with a mitochondrial-targeted NHE1 expression vector (pmitoNHE1). Mitochondrial membrane potential was expressed as JC-1 aggregate/monomer fluorescence. Mitochondrial pH was measured using a mitochondrial-targeted pH sensor. Data are expressed as means ± SEM and are compared with Student´s t-test.Results: Mitochondrial NHE1 overexpression resulted in increased mitochondrial membrane potential, similar to our observations in obese and diabetic mitochondria (0,6140 in control vs 0,7561 in pmitoNHE1 cells, p