The effect of short-term methionine restriction on glutathione synthetic capacity and antioxidant responses at the whole tissue and mitochondrial level in the rat liver.

Dietary methionine restriction (MR) where methionine is the sole source of sulfur amino acid increases lifespan in diverse species. Methionine restricted rodents experience a decrease in glutathione (GSH), a major antioxidant, in several tissues, which is paradoxical to longevity interventions because tissues with low GSH might experience more oxidative damage. Liver plays a key role in GSH synthesis and here we examined how MR influences GSH metabolism in the liver.

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).

Multidimensional mitochondrial energetics: Application to the study of electron leak and hydrogen peroxide metabolism.

Oxygen consumption is a valuable tool to link with measurements of mitochondrial electron leakage to form reactive oxygen species (ROS), which in mitochondria is predominantly superoxide and HO. However, oxygen consumption may respond differently to changes in conditions than superoxide/HO production does, complicating the use of respiration as a sole indicator of mitochondrial energetics. The same equipment that is valuable for fluorescent monitoring of HO efflux provides a straightforward means of estimating membrane potential (ΔΨ), thereby an alternative metric of mitochondrial energetics is readily added to complement studies on the link between mitochondrial energetics and electron leak.