title: Mitochondrial NHE1: a newly identified target to prevent heart disease.
abstract: Mitochondrial damage has been associated with early steps of cardiac dysfunction in heart subjected to ischemic stress, oxidative stress and hypertrophy. A common feature for the mitochondrial deterioration is the loss of the mitochondrial membrane potential (ΔΨ m) with the concomitant irreversible opening of the mitochondrial permeability transition pore (MPTP) which follows the mitochondrial Ca(2+) overload, and the subsequent mitochondrial swelling. We have recently characterized the expression of the Na(+)/H(+) exchanger 1 (mNHE1) in mitochondrial membranes. This surprising observation provided a unique target for the prevention of the Ca(2+)-induced MPTP opening, based on the inhibition of the NHE1 m. In this line, inhibition of NHE1 m activity and/or reduction of NHE1 m expression decreased the Ca(2+)-induced mitochondrial swelling and the release of reactive oxygen species (ROS) in isolated cardiac mitochondria and preserved the ΔΨ m in isolated cardiomyocytes. Mitochondrial NHE1 thus represents a novel target to prevent cardiac disease, opening new avenues for future research.
authors.affiliation: Centro de Investigaciones Cardiovasculares, Consejo Nacional de Investigaciones Científicas y Técnicas Facultad de Ciencias Médicas, Universidad Nacional de La Plata La Plata, Argentina.
authors.forename: Bernardo V
authors.initials: BV
authors.lastname: Alvarez
authors.forename: María C
authors.initials: MC
authors.lastname: Villa-Abrille
keywords: NHE1; ischemia; mitochondrial permeability transition pore; mitochondrial swelling; siRNA