An integrated mitochondrial ROS production and scavenging model: implications for heart failure.

ABSTRACT: It has been observed experimentally that cells from failing hearts exhibit elevated levels of reactive oxygen species (ROS) upon increases in energetic workload. One proposed mechanism for this behavior is mitochondrial Ca(2+) mismanagement that leads to depletion of ROS scavengers. Here, we present a computational model to test this hypothesis. Previously published models of ROS production and scavenging were combined and reparameterized to describe ROS regulation in the cellular environment. Extramitochondrial Ca(2+) pulses were applied to simulate frequency-dependent changes in cytosolic Ca(2+). Model results show that decreased mitochondrial Ca(2+)uptake due to mitochondrial Ca(2+) uniporter inhibition (simulating Ru360) or elevated cytosolic Na(+), as in heart failure, leads to a decr

SUBMITTER: Gauthier LD 

PROVIDER: S-EPMC3882515 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature