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

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 γ coactivator 1α (PGC-1α) show reductions in expression of myelin-related proteins and exhibit myelin-associated lesions, so we identified PGC-1α target genes in Schwann cells (SCs) in vitro to determine potential roles for PGC-1α in glia and tested whether PGC-1α was sufficient for SC differentiation and myelination. Forskolin-induced differentiation was associated with an upregulation of PGC-1α mRNA and protein, and while overexpression of PGC-1α upregulated genes such as manganese superoxide dismutase and estrogen-related receptor α, it was not sufficient for induction of differentiation. Both PGC-1α overexpression and forskolin exposure caused an increase in the mitochondrial fusion-related protein mitofusin 1. These studies suggest that PGC-1α might be a potential target to promote mitochondrial stability during differentiation and myelination.