Mitochondrial NHE1: a newly identified target to prevent heart disease

• Autores: Álvarez, Bernardo Víctor; Villa Abrille, María Celeste
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: reseña artículo
• Materia: Ciencias Médicas; Ischemia; Mitochondrial permeability transition pore; Mitochondrial swelling; NHE1; Sirna
• Institución: Universidad Nacional de La Plata

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 (δψm) with the concomitant irreversible opening of the mitochondrial permeability transition pore (MPTP) which follows the mitochondrial Ca²⁺ 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 Ca²⁺-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 Ca²⁺-induced mitochondrial swelling and the release of reactive oxygen species (ROS) in isolated cardiac mitochondria and preserved the δψm in isolated cardiomyocytes. Mitochondrial NHE1 thus represents a novel target to prevent cardiac disease, opening new avenues for future research.
Facultad de Ciencias Médicas
Centro de Investigaciones Cardiovasculares