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

The protein kinase C delta (PKCδ) 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 PKCδ 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 PKCδ 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 PKCδ protein expression. We hypothesize that the lack of PKCδ within this higher molecular weight complex may contribute to defective mitochondrial PKCδ signaling and thus to the bioenergetic defects observed in BTHS.