Fig. 5: Schematic model of GSNOR function in skeletal muscle differentiation and homeostasis.

Our data indicate that GSNOR and nNOS are co-expressed and reasonably part of the same complex (co-immunoprecipitate) during myogenesis. In this way, they sustain differentiation (left). Co-immunoprecipitation and co-localization analyses indicate that GSNOR and nNOS might be recruited in the same complex close to the sarcolemma. This, along with the correct activation of NO/cGMP signaling induced by sarcolemmatic nNOS, should allow the nitrosylation of specific targets (e.g. RyR1) and contribute to the correct physiology of the skeletal muscle (e.g., vasodilation and regeberation) (middle). During aging, or in dystrophic muscles, GSNOR levels are found to be reduced and, coherently, the extent of S-nitrosylated protein (PSNO) increased (right). GSNOR decrease is a hallmark of patho-physiological states associated with muscle wasting. However, we still do not know if this event is associated with nNOS translocation into the sarcoplasm, as reported in different pathological models of atrophy. Although reasonable, so far there is no evidence supporting this hypothesis