d-Galactose toxicity in mice is associated with mitochondrial dysfunction: protecting effects of mitochondrial nutrient R-alpha-lipoic acid

d-Galactose (d-gal) -induced aging models in Drosophila, houseflies, mice and rats have been widely used; however, the underlying mechanisms are poorly understood. To investigate the involvement of mitochondrial dysfunction of d-gal, mitochondrial function was examined in the brain and liver of C57BL/6J mice, subjected to a treatment of d-gal with or without a concomitant treatment with a mitochondrial nutrient, R-alpha-lipoic acid (LA). d-Gal treatment induced a significant decrease in succinate-linked respiratory control ratio (RCR) and ADP/O ratio in the liver and brain, and also a significant increase in the maximum velocity (Vmax) and substrate binding affinity (Km) of complex II in the liver. LA treatment to d-gal-injected animals restored mitochondrial RCR in both brain and liver, ADP/O and Km of complex II in the liver. These results suggest LA is effective in delaying d-gal toxicity by ameliorating mitochondrial dysfunction.