An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases

Abstract

Neuromuscular diseases (NMDs) are dysfunctions that involve skeletal muscle and cause incorrect communication between the nerves and muscles. The specific causes of NMDs are not well known, but most of them are caused by genetic mutations. NMDs are generally progressive and entail muscle weakness and fatigue. Muscular impairments can differ in onset, severity, prognosis, and phenotype. A multitude of possible injury sites can make diagnosis of NMDs difficult. Mitochondria are crucial for cellular homeostasis and are involved in various metabolic pathways; for this reason, their dysfunction can lead to the development of different pathologies, including NMDs. Most NMDs due to mitochondrial dysfunction have been associated with mutations of genes involved in mitochondrial biogenesis and metabolism. This review is focused on some mitochondrial routes such as the TCA cycle, OXPHOS, and β-oxidation, recently found to be altered in NMDs. Particular attention is given to the alterations found in some genes encoding mitochondrial carriers, proteins of the inner mitochondrial membrane able to exchange metabolites between mitochondria and the cytosol. Briefly, we discuss possible strategies used to diagnose NMDs and therapies able to promote patient outcome.

Generation of a Yeast Cell Model Potentially Useful to Identify the Mammalian Mitochondrial N-Acetylglutamate Transporter

“…However, a significant number of them still need to be discovered. The functional identification of this group of proteins is of the utmost importance because their mutation can cause human diseases [32,63]. The biochemical characterization of these transporters facilitates their association with clinical alterations found in patients.…”

Diaphragm Fatigue in SMNΔ7 Mice and Its Molecular Determinants: An Underestimated Issue

“…In the present study, a significant increase in Ser637 phosphorylation of DRP1 was found (Figure 5b), suggesting an alteration in mitochondrial shape. Fused mitochondria have been demonstrated in aging [33,34], under nutrient deprivation [35], and in neuromuscular disease [36,37]. In-depth morphological studies are necessary to verify the presence of fused/elongated mitochondria in SMA diaphragm.…”

Protein Transduction Domain-Mediated Delivery of Recombinant Proteins and In Vitro Transcribed mRNAs for Protein Replacement Therapy of Human Severe Genetic Mitochondrial Disorders: The Case of Sco2 Deficiency

“…The overall estimated prevalence of these disorders is one to three cases per 20,000 individuals [ 24 ], with lifelong symptoms that can appear from very early (newborn) to later in life. Unsurprisingly, mitochondrial disorders often affect organs with high metabolic needs such as muscles, heart, liver, kidneys, central nervous system (CNS), peripheral nervous system (PNS), as well sensory organs (eyes and ears) [ 13 , 25 ]. It has been reported that some mitochondrial disorders can affect only a single organ (as in Leber hereditary optic neuropathy (LHON) [ 26 ] and in mitochondrial non-syndromic hearing loss and deafness), but often, these disorders cause multi-system dysfunction.…”