Mitochondria can act as energy-sensing regulators of hydrogen peroxide availability.

Mitochondria are widely recognized as sources of reactive oxygen species in animal cells, with HO being of particular note because it can act not only in oxidative stress but also is important to several signalling pathways. Lesser recognized is that mitochondria can have far greater capacity to consume HO than to produce it; however, the consumption of HO may be kinetically constrained by HO availability especially at the low nanomolar (or lower) concentrations that occur in vivo. The production of HO is a function of many factors, not the least of which are respiratory substrate availability and the protonmotive force (Δp). The Δp, which is predominantly membrane potential (ΔΨ), can be a strong indicator of mitochondrial energy status, particularly if respiratory substrate supply is either not meeting or exceeding demand. The notion that mitochondria may functionally act in regulating HO concentrations may be somewhat implicit but little evidence demonstrating this is available. Here we demonstrate key assumptions that are required for mitochondria to act as regulators of HO by an integrated system of production and concomitant consumption. In particular we show the steady-state level of HO mitochondria approach is a function of both mitochondrial HO consumption and production capacity, the latter of which is strongly influenced by ΔΨ. Our results are consistent with mitochondria being able to manipulate extramitochondrial HO as a means of signalling mitochondrial energetic status, in particular the Δp or ΔΨ. Such a redox-based signal could operate with some independence from other energy sensing mechanisms such as those that transmit information using the cytosolic adenylate pool.