Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres

Gabriela Silva Rodrigues, Rosely Oliveira Godinho, Beatriz Hitomi Kiyomoto, Juliana Gamba, Acary Souza Bulle Oliveira, Beny Schmidt, and  Célia Harumi Tengan

Sci Rep. 2016; 6: 20780. 

doi: 10.1038/srep20780


Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events.

Programa de Pós-Graduação em Neurologia/ Neurociências

Rua Napoleão de Barros, 626

E-mail: ppgneurologia@unifesp.br / ppgneuro.unifesp@gmail.com