Involvement of protein kinase C delta in the alteration of mitochondrial mass in human cells under oxidative stress

Alteration of mitochondrial mass of human 143B osteosarcorna cells upon exposure to hydrogen peroxide (H2O2) was investigated. We found that mitochondrial mass and the intracellular level of H2O2 were increased by exogenous H2O2, which was accompanied with up-regulation of functional PKC delta. To investigate the role of PKC delta in H2O2-induced increase of mitochondrial mass, we treated 143B cells with PKC delta activator, bistratene A, and PKC delta inhibitor, rottlerin, respectively. The results show that bistratene A caused an increase of mitochondrial mass and that the H2O2-induced increase of mitochondrial mass was completely suppressed by rottlerin. Furthermore, we found that activation of PKC delta by bistratene A increased the intracellular levels of H2O2 and MnSOD protein expression. By contrast, suppression of PKC delta by rottlerin decreased the intracellular levels of H2O2 and MnSOD protein expression. Moreover, we noted that MnSOD expression was highly correlated with the expression of p53, which was controlled by PKC delta. Finally, we demonstrated that PKC delta was overexpressed in skin fibroblasts of patients with MERRF syndrome. Taken together, we conclude that PKC delta is involved in the regulation of mitochondrial mass and intracellular H2O2 in human cells and may play a key role in the overproliferation of mitochondria in the affected tissues of patients with mitochondrial diseases such as MERRF syndrome. (c) 2006 Elsevier Inc. All rights reserved.