The multifaceted role of nitric oxide synthases in mitochondrial biogenesis and cell differentiation

Nitric oxide (NO) is physiologically synthetized by a family of enzymes called NO synthases (NOSs). NO is a pleiotropic second messenger having a fundamental role in several cellular processes including cell differentiation. Being a high reactive molecule, NO must be synthetized in close proximity to the effector/target. For this reason, the subcellular localization of NOSs is tightly regulated by different post-translation mechanisms. Recently, in murine C2C12 myoblasts, we have demonstrated that mitochondrial biogenesis, an essential event for cell differentiation, can be effective only if the site of NO production is located at nuclear level, where NO favors the CREB-dependent expression of PGC-1a gene. The increase of NO flux in nuclei is elicited by the up-regulation and redistribution of neuronal NOS (nNOS) toward nuclei.