Acetyl-l-Carnitine Activates the Peroxisome Proliferator-Activated Receptor-γ Coactivators PGC-1α/PGC-1β–Dependent Signaling Cascade of Mitochondrial Biogenesis and Decreases the Oxidized Peroxiredoxins Content in Old Rat Liver

Abstract The behavior of the peroxisome proliferator-activated receptor-γ coactivators PGC-1α/PGC-β—dependent mitochondrial biogenesis signaling pathway, as well as the level of some antioxidant enzymes and proteins involved in mitochondrial dynamics in the liver of old rats before and after 2 months of acetyl-l-carnitine (ALCAR) supplementation, was tested. The results reveal that ALCAR treatment is able to reverse the age-associated decline of PGC-1α, PGC-1β, nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (ND1), and cytochrome c oxidase subunit IV (COX IV) protein levels, of mitochondrial DNA (mtDNA) content, and of citrate synthase activity. Moreover, it partially reverses the mitochondrial superoxide dismutase 2 (SOD2) decline and reduces the cellular content of oxidized peroxiredoxins. These data demonstrate that ALCAR treatment is able to promote in the old rat liver a new mitochondrial population th...