Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 498, Issue 1, Pages 214-220Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.02.208
Keywords
Reactive oxygen species; Mitochondria; Complex I; lschemia-reperfusion; Heart; NDUFS4
Categories
Funding
- Memorial University of Newfoundland Institutional Multi-Disciplinary, Seed, and Bridge Fund [211208 46304 2000]
- Research Development Corporation (RDC) of Newfoundland [5404.1980.102]
- Queen Elizabeth Diamond Jubilee Scholarship
Ask authors/readers for more resources
Recent work has found that complex I is the sole source of reactive oxygen species (ROS) during myocardial ischemia-reperfusion (IR) injury. However, it has also been reported that heart mitochondria can also generate ROS from other sources in the respiratory chain and Krebs cycle. This study examined the impact of partial complex I deficiency due to selective loss of the Ndufs4 gene on IR injury to heart tissue. Mice heterozygous for NDUFS4 (NDUFS4+/-) did not display any significant changes in overall body or organ weight when compared to wild-type (WT) littermates. There were no changes in superoxide (O-2(center dot-))/hydrogen peroxide (H2O2) release from cardiac or liver mitochondria isolated from NDUFS4 mice. Using selective ROS release inhibitors, we found that complex III is a major source of ROS in WT and NDUFS4 +/- cardiac mitochondria respiring under state 4 conditions. Subjecting hearts from NDUFS4 +/- mice to reperfusion injury revealed that the partial loss of complex I decreases contractile recovery and increases myocardial infarct size. These results correlated with a significant increase in O-2(center dot-)/H2O2 release rates in mitochondria isolated from NDUFS4 +/- hearts subjected to an IR challenge. Taken together, these results demonstrate that the partial absence of complex I sensitizes the myocardium towards IR injury and that the main source of ROS following reperfusion is complex III. (C) 2018 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available