Mitochondrial diseases

Abstract

Mitochondrial diseases are a group of genetic disorders that are characterized by defects in oxidative phosphorylation and caused by mutations in genes in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) that encode structural mitochondrial proteins or proteins involved in mitochondrial function. Mitochondrial diseases are the most common group of inherited metabolic disorders and are among the most common forms of inherited neurological disorders. One of the challenges of mitochondrial diseases is the marked clinical variation seen in patients, which can delay diagnosis. However, advances in next-generation sequencing techniques have substantially improved diagnosis, particularly in children. Establishing a genetic diagnosis allows patients with mitochondrial diseases to have reproductive options, but this is more challenging for women with pathogenetic mtDNA mutations that are strictly maternally inherited. Recent advances in in vitro fertilization techniques, including mitochondrial donation, will offer a better reproductive choice for these women in the future. The treatment of patients with mitochondrial diseases remains a challenge, but guidelines are available to manage the complications of disease. Moreover, an increasing number of therapeutic options are being considered, and with the development of large cohorts of patients and biomarkers, several clinical trials are in progress.

An energetic view of stress: Focus on mitochondria

“…For example, individuals with genetic mitochondrial disorders due to inherited mtDNA mutations, which impair respiratory chain function, suffer from debilitating and often lethal symptoms (Gorman et al, 2016). Organisms with excessive mitochondrial dysfunction are incapable to sustain life and to adapt to dietary and physiological perturbations.…”

Recent Advances in Mitochondrial Disease

“…There remain many challenges in our understanding of mitochondrial diseases, as highlighted in a recent review (28). Although our ability to obtain a genetic diagnosis has vastly improved (see below), there remains little in the way of effective treatment.…”

“…These disorders are clinically diverse and can manifest in the neonatal phase, childhood, or adulthood (28). Given that mitochondria are present in all cells of the body with the exception of red blood cells, the resulting clinical symptoms can present in isolated organs, but they often occur with multiple system involvement in organs with high energy demands, such as the brain, skeletal muscles, and heart (28). Often there are limited genotype-phenotype correlations to direct molecular genetic diagnosis, and many phenotypes can be caused by defects involving numerous different genes.…”

“…The majority of these proteins are encoded by nuclear DNA (nDNA), but 13 are encoded by mitochondrial DNA (mtDNA); consequently, mitochondria are under the dual genetic control of both the mitochondrial and nuclear genomes. Reflecting their diverse functions, only ∼150 mitochondrial proteins are directly involved in oxidative phosphorylation and ATP production (28). The remaining mitoproteome components include proteins involved in the assembly of the complexes, the maintenance and expression of mtDNA, intraorganellar protein synthesis, and mitochondrial dynamics (57).…”

Multippel sklerose – en mitokondriemediert sykdom?

“…Mitokondriesykdommer er blant de hyppigste arvelige metabolske sykdommer, og mange av disse rammer hjernen (5,6). I tillegg spiller mitokondrier en viktig rolle ved nevrodegenerative tilstander, som for eksempel Parkinsons sykdom (7).…”