Mitochondrial NHE1 Na+/H+ exchanger: A newly identified target to prevent heart disease

ALVAREZ BV; VILLA ABRILLE MC

Frontiers in physiology

Lausanne : Frontiers Research Foundation

Año: 2013

1664-042X

Mitochondrial damage has been associated with early steps of cardiac dysfunction inheart subjected to ischemic stress, oxidative stress and hypertrophy. A common featurefor the mitochondrial deterioration is the loss of the mitochondrial membrane potential(=>m) with the concomitant irreversible opening of the mitochondrial permeabilitytransition pore (MPTP) which follows the mitochondrial Ca2+ overload, and thesubsequent mitochondrial swelling. We have recently characterized the expression ofthe NHE1 Na+/H+ exchanger (NHE1m) in mitochondrial membranes. This surprisingobservation provided a unique target for the prevention of the Ca2+-induced MPTPopening, based on the inhibition of the NHE1m. In this line, inhibition of NHE1mactivity and/or reduction of NHE1m expression, decreased the Ca2+-inducedmitochondrial swelling and the release of reactive oxygen species in isolated cardiacmitochondria, and preserved the =>m in isolated cardiomyocytes. Mitochondrial NHE1thus represents a novel target to prevent cardiac disease, opening new avenues for futureresearch.