Review: Using isolated mitochondria to investigate mitochondrial hydrogen peroxide metabolism.

Mitochondria are recognized as centrally important to cellular reactive oxygen species (ROS), both as a potential source and due to their substantial antioxidant capacity. While much of the initial ROS formed by mitochondria is superoxide, this is rapidly converted to hydrogen peroxide (H2O2) which more readily crosses membranes making H2O2 important in both redox signalling mechanisms and conditions of oxidative stress. Here I outline our studies on mitochondrial H2O2 metabolism with a focus on some of the challenges and strategies involved with developing an integrated model of mitochondria being intrinsic regulators of H2O2. This view of mitochondria as regulators of H2O2 goes beyond the simpler contention of them being net producers or consumers. Moreover, the integration of both consumption and production can then be tied to a putative mechanism linking energy sensing at the level of the mitochondrial protonmotive force. This mechanism would provide a means of mitochondria communicating their energetic status the extramitochondrial compartment via local H2O2 concentrations. I conclude by explaining how these concepts developed using rodent muscle as a model have high relevance and applicability to comparative studies.