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

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.

Nitric oxide synthesis is increased in cybrid cells with m.3243A>G mutation.

Nitric oxide (NO) is a free radical and a signaling molecule in several pathways, produced by nitric oxide synthase (NOS) from the conversion of L-arginine to citrulline. Supplementation of L-arginine has been used to treat MELAS (mitochondrial encephalopathy with lactic acidosis and stroke like syndrome), a mitochondrial disease caused by the m.3243A>G mutation.

The mutations m.5628T>C and m.8348A>G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia.

We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNA(Ala) (m.5628T>C) and tRNA(Lys) (m.8348A>G) genes.

The role of nitric oxide in muscle fibers with oxidative phosphorylation defects.

NO has been pointed as an important player in the control of mitochondrial respiration, especially because of its inhibitory effect on cytochrome c oxidase (COX). However, all the events involved in this control are still not completely elucidated. We demonstrate compartmentalized abnormalities on nitric oxide synthase (NOS) activity on muscle biopsies of patients with mitochondrial diseases.