Abstract
We investigated the biogenesis and mitochondrial antioxidant capacity of cytochrome c oxidase (COX) within the skeletal muscle under the treatments of p53 inhibitors (pifithrin, PFT alpha and PFT mu). Significantly, PFT mu increased mtDNA content and COX biogenesis. These changes coincided with increases in the activity and expression of manganese superoxide dismutase (MnSOD), the key antioxidant enzyme in mitochondria. Conversely, PFT alpha caused muscle loss, increased oxidative damage and decreased MnSOD activity in intermyofibrillar (IMF) mitochondria. Mechanically, PFT mu inhibited p53 translocation to mitochondria and thus increased its transcriptional activity for expression of synthesis of cytochrome c oxidase 2 (SCO2), an important assembly protein for COX. This study provides in vivo evidence that PFT mu, superior to PFT alpha, preserves muscle mass and increases mitochondrial antioxidant activity. (C) 2012 Elsevier B.V. and Mitochondria Research Society. All rights reserved.