FIGURE 9.

Schematic representation of the role of nuclear nNOS and α-Syntrophin in mitochondrial biogenesis. A, PDZ-containing nNOS (fl-nNOS) is located at the plasma membrane and is part of the Dystrophin complex via the anchoring to α-Syntrophin. PDZ-lacking nNOS (nNOSβ) maintains full NO synthetizing activity and localizes in the cytoplasm but not in the nucleus. B, the Dystrophin complex also localizes at the inner membrane of the nuclear envelope (58), and fl-nNOS is recruited into the nucleus via its interaction with α-Syntrophin. Under certain stimuli (e.g., induction of myogenesis), the PDZ domain is responsible for α-Syntrophin-mediated fl-nNOS recruitment to the nucleus and allows NO synthesis directly at the nuclear level. C, this process facilitates S-nitrosylation of nuclear proteins including CREB transcription factor, which binds to PGC-1α promoter and induces mitochondrial biogenesis. During myogenesis, nuclear fl-nNOS and α-Syntrophin content increases in the nucleus, and this triggers mitochondrial biogenesis. SGs, sarcoglycans; DGs, dystroglycans; NRF1/2, nuclear respiratory factor 1 or 2.