Role of mitochondrial deficits in the onset of neuromuscular diseases

Neuromuscular diseases (NMDs) include genetically determined or acquired pathologies involving several components of the motor unit, they result in incorrect signal propagation between motor neurons and muscles or a complete loss of communication between them.1 NMDs can be divided into two main groups: muscle and nerve diseases. The former cause a direct loss of muscle function, while the latter involve an indirect loss of nerve function, which in turn impairs muscle activity. Symptoms are usually progressive and differ in onset, severity, prognosis, and phenotype. Diagnosis is complicated due to a variety of probable injury sites. The specific causes of NMDs are not well understood. Many NMDs arise from mitochondrial dysfunction, and are associated with mutations in genes implicated in mitochondrial metabolism and biogenesis.2 Mitochondrial pathways including the tricarboxylic acid cycle, oxidative phosphorylation, and beta-oxidation were found to be altered in NMDs, implying defects in energy supply and leading to impaired muscle and moto neurons functions. The loss of mitochondrial functions also impairs signal transmission in the nervous system, as well as the synthesis and release of neurotransmitters. Mutations were also found in some genes encoding mitochondrial carrier proteins necessary to exchange metabolites between the cytosol and the mitochondrial matrix. Understanding the link between impaired mitochondrial metabolism and NMDs is essential to identify new biomarkers and tools for early diagnosis, as well as to develop new therapeutic strategies and drugs able to improve patients’ quality of life.