In (skeletal) muscle cells, PGC-1 signaling controls mitochondrial biogenesis and oxidative substrate metabolism. PGC-1 signaling disturbance in skeletal muscle is linked to several chronic diseases. This pathway depicts the mechanism in which inhibition of GSK-3β increases Pgc-1α abundance, through dephosphorylation of Tfeb [Theeuwes et al, 2019](https://doi.org/10.1016/j.bbamcr.2019.118610). This reaction allows Tfeb to translocate to the nucleus, where it stimulates the transcription of the PPARGC1A gene to the Pgc-1α protein. Phosphorylation of Tfeb leads to binding with members of the 14-3-3 protein family, which disables transport into the nucleus. If the dephosphorylation of Tfeb through Gsk-3β is a direct or indirect reaction is as of yet unknown.