H2O2 metabolism in liver and heart mitochondria: Low emitting-high scavenging and high emitting-low scavenging systems.

Citation:
Kamunde, C., M. Sharaf, and N. MacDonald, "H2O2 metabolism in liver and heart mitochondria: Low emitting-high scavenging and high emitting-low scavenging systems.", Free radical biology & medicine, vol. 124, pp. 135-148, 2018 May 24.

Abstract:

Although mitochondria are presumed to emit and consume reactive oxygen species (ROS), the quantitative interplay between the two processes in ROS regulation is not well understood. Here, we probed the role of mitochondrial bioenergetics in HO metabolism using rainbow trout liver and heart mitochondria. Both liver and heart mitochondria emitted HO at rates that depended on their metabolic state, with the emission rates (free radical leak) constituting 0.8-2.9% and 0.2-2.5% of the respiration rate in liver and heart mitochondria, respectively. When presented with exogenous HO, liver and heart mitochondria consumed it by first order reactions with half-lives (s) of 117 and 210, and rate constants of 5.96 and 3.37 (× 10 s), respectively. The mitochondrial bioenergetic status greatly affected the rate of HO consumption in heart but not liver mitochondria. Moreover, the activities and contribution of HO scavenging systems varied between liver and heart mitochondria. The significance of the scavenging systems ranked by the magnitude (%) of inhibition of HO removal after correcting for emission were, liver (un-energized and energized): catalase > glutathione (GSH) ≥ thioredoxin reductase (TrxR); un-energized heart mitochondria: catalase > TrxR > GSH and energized heart mitochondria: GSH > TrxR > catalase. Notably, depletion of GSH evoked a massive surge in HO emission that grossly masked the contribution of this pathway to HO scavenging in heart mitochondria. Irrespective of the organ of their origin, mitochondria behaved as HO regulators that emitted or consumed it depending on the ambient HO concentration, mitochondrial bioenergetic state and activity of the scavenging enzyme systems. Indeed, manipulation of mitochondrial bioenergetics and HO scavenging systems caused mitochondria to switch from being net consumers to net emitters of HO. Overall, our data suggest that the low levels of HO typically present in cells would favor emission of this metabolite but the scavenging systems would prevent its accumulation.