Methionine and homocysteine modulate the rate of ROS generation of isolated mitochondria in vitro

Dietary methionine restriction and supplementation in mammals have beneficial (antiaging) and detrimental effects respectively, which have been related to chronic modifications in the rate of mitochondrial ROS generation. However it is not known if methionine or its metabolites can have, in addition, direct effects on the rate of mitochondrial ROS production. This is studied here for the methionine cycle metabolites S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), homocysteine and methionine itself in isolated rat liver, kidney, heart, and brain mitochondria. The results show that methionine increases ROS production in liver and kidney mitochondria, homocysteine increases it in kidney and decreases it in the other three organs, and SAM and SAH have no effects. The variations in ROS production are localized at complexes I or III. These changes add to previously described chronic effects of methionine restriction and supplementation in vivo.