Reduced protein kinase C delta association with a higher molecular weight complex in mitochondria of Barth Syndrome lymphoblasts

Abstract

The protein kinase C delta (PKC{delta}) signalosome exists as a high molecular weight complex in mitochondria and controls mitochondrial oxidative phosphorylation. Barth Syndrome (BTHS) is a rare X-linked genetic disease in which mitochondrial oxidative phosphorylation is impaired due to a mutation in the gene TAFAZZIN which results in reduction in the phospholipid cardiolipin and an accumulation of monolysocardiolipin. Here we examined if PKC{delta} association with a higher molecular weight complex was altered in mitochondria of BTHS lymphoblasts. Immunoblot analysis of blue native-polyacrylamide gel electrophoresis mitochondrial fractions revealed that PKC{delta} associated with a higher molecular weight complex in control lymphoblasts but this was markedly reduced in BTHS patient B lymphoblasts in spite of an increase in PKC{delta} protein expression. We hypothesize that the lack of PKC{delta} within this higher molecular weight complex may contribute to defective mitochondrial PKC{delta} signaling and thus to the bioenergetic defects observed in BTHS.