Regulation of PGC-1alpha and PGC-1alpha-responsive genes with forskolin-induced Schwann cell differentiation

Abstract

Recent evidence indicates that mitochondrial homeostasis is critical for myelination and maintenance of peripheral nerve function. Mice lacking the metabolic transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator 1alpha (PGC-1alpha) show reductions in expression of myelin-related proteins and exhibit myelin-associated lesions, so we identified PGC-1alpha target genes in Schwann cells (SCs) in vitro to determine potential roles for PGC-1alpha in glia and tested whether PGC-1alpha was sufficient for SC differentiation and myelination. Forskolin-induced differentiation was associated with an upregulation of PGC-1alpha mRNA and protein, and while overexpression of PGC-1alpha upregulated genes such as manganese superoxide dismutase and estrogen-related receptor alpha, it was not sufficient for induction of differentiation. Both PGC-1alpha overexpression and forskolin exposure caused an increase in the mitochondrial fusion-related protein mitofusin 1. These studies suggest that PGC-1alpha might be a potential target to promote mitochondrial stability during differentiation and myelination.