In recent years, the roles of mitochondrial RNA and its associated human diseases have been reported to increase significantly. Treatments based on mtRNA metabolic processes and nuclear gene mutations are thus discussed. The mitochondrial oxidative phosphorylation process is affected by mtRNA metabolism, including mtRNA production, maturation, stabilization, and degradation, which leads to a variety of inherited human mitochondrial diseases. Moreover, mitochondrial diseases are caused by mitochondrial messenger RNA, mitochondrial transfer RNA, and mitochondrial ribosomal RNA gene mutations. This review presents the molecular mechanisms of human mtRNA metabolism and pathological mutations in mtRNA metabolism-related nuclear-encoded/nonencoded genes and mitochondrial DNA mutations to highlight the importance of mitochondrial RNA-related diseases and treatments.
Humans ; Mitochondrial Diseases/therapy* ; RNA, Mitochondrial ; RNA/genetics* ; Mitochondria/genetics* ; Mutation/genetics* ; RNA, Transfer/genetics* ; DNA, Mitochondrial/genetics*

Humans ; Mitochondrial Diseases/therapy* ; DNA, Mitochondrial/genetics*

Alzheimer Disease ; complications ; pathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Humans ; Mitochondria ; physiology ; Mitochondrial Diseases ; etiology ; tau Proteins ; metabolism

Diffuse Cerebral Sclerosis of Schilder ; diagnosis ; therapy ; Epilepsy ; etiology ; therapy ; Humans ; Mitochondrial Diseases ; complications

The aim of this study was to investigate the clinical features and DGUOK gene mutations of an infant with mitochondrial DNA depletion syndrome (MDS). The patient (more than 7 months old) manifested as hepatosplenomegaly, abnormal liver function, nystagmus and psychomotor retardation. Genetic DNA was extracted from peripheral blood samples of the patient and her parents. Targeted Exome Sequencing was performed to explore the genetic causes. Sanger sequencing was carried out to confirm the detected mutations. The sequencing results showed that the patient was a compound heterozygote for c.679G>A and c.817delT in the DGUOK gene. The former was a reportedly pathogenic missense mutation of maternal origin, while the latter, a frameshift mutation from the father, has not been described yet. The findings in this study expand the mutation spectrum of DGUOK gene, and provide molecular evidence for the etiologic diagnosis of the patient as well as for the genetic counseling and prenatal diagnosis in the family.
Female ; Humans ; Infant ; Mitochondrial Diseases ; genetics ; therapy ; Mutation ; Phosphotransferases (Alcohol Group Acceptor) ; chemistry ; genetics

Apoptosis ; Cell Nucleus ; metabolism ; Clinical Trials as Topic ; Cytoplasm ; metabolism ; DNA, Mitochondrial ; metabolism ; Glucocorticoids ; therapeutic use ; Humans ; MELAS Syndrome ; drug therapy ; Mitochondria ; metabolism ; Mitochondrial Diseases ; drug therapy ; Muscular Diseases ; drug therapy

Many researchers have reported that oxidative damage to mitochondrial DNA (mtDNA) is increased in several age-related disorders. Damage to mitochondrial constituents and mtDNA can generate additional mitochondrial dysfunction that may result in greater reactive oxygen species production, triggering a circular chain of events. However, the mechanisms underlying this vicious cycle have yet to be fully investigated. In this review, we summarize the relationship of oxidative stress-induced mitochondrial dysfunction with mtDNA mutation in neurodegenerative disorders.
Animals ; DNA, Mitochondrial/*genetics ; Humans ; Mitochondria/drug effects/genetics/metabolism ; Molecular Targeted Therapy ; *Mutation ; Neurodegenerative Diseases/drug therapy/*genetics/metabolism ; Reactive Oxygen Species/metabolism

Nuclease-based gene editing technologies have opened up opportunities for correcting human genetic diseases. For the first time, scientists achieved targeted gene editing of mitochondrial DNA in mouse oocytes fused with patient cells. This fascinating progression may encourage the development of novel therapy for human maternally inherent mitochondrial diseases.
Animals ; DNA, Mitochondrial ; genetics ; Embryo, Mammalian ; metabolism ; Genome ; Germ Cells ; metabolism ; Humans ; Mitochondrial Diseases ; genetics ; therapy ; RNA Editing ; genetics

Alkyl and Aryl Transferases ; genetics ; Child ; DNA, Mitochondrial ; genetics ; Fibroblasts ; metabolism ; Glomerulosclerosis, Focal Segmental ; diagnosis ; drug therapy ; genetics ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; genetics ; Mitochondrial Diseases ; diagnosis ; drug therapy ; genetics ; Mutation ; Nephrotic Syndrome ; diagnosis ; drug therapy ; genetics ; Protein Kinases ; genetics ; Ubiquinone ; analogs & derivatives ; biosynthesis ; deficiency ; therapeutic use

The purpose of the present study was to investigate the effects of icariin (ICA) on the content of beta-amyloid (Abeta) and the expression of neurotrophic factors in the brain of mitochondrial deficiency model rats. SD rats were infused subcutaneously with sodium azide, which is an inhibitor of mitochondrial respiratory chain complex IV, via a minipump (0. 5 mg . kg-1 h-1) for 28 days to establish the mitochondrial deficiency animal model. The activity of mitochondrial respiratory chain complex IV (i. e. cytochrome C oxidase, COX) in hippocampus was measured by biochemical methods. ELISA method was used to detect the content of Abeta in the brain. The expression of neurotrophic factors was detected by Western blot and immunohistochemistry methods. Image analysis was performed by Image-pro software. The results showed that chronic infusion of sodium azide by minipump induced a significant decrease in the activity of mitochondrial cytochrome C oxidase, an obvious increase in the content of Abeta, and a marked decline in the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the brain of rats. Intragastrical administration of ICA (12 or 36 mg . kg-l) significantly ameliorated all these abnormalities in the model rats. In conclusion, ICA can increase mitochondrial activity, inhibit Abeta production, and enhance the expression of neurotrophic factors in the brain of model rats induced by sodium azide. The results suggested that ICA may have beneficial prospect for the treatment of Alzheimer's disease.
Amyloid ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Brain-Derived Neurotrophic Factor ; metabolism ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Flavonoids ; pharmacology ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; pathology ; Mitochondrial Diseases ; drug therapy ; metabolism ; Nerve Growth Factor ; metabolism ; Nerve Growth Factors ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; metabolism