Mitochondria and mitochondrial nitric oxide synthase alterations participate in energetical dysbalance, aging and age-related diseases.
Nitric oxide (NO) is a unique mediator of cellular regulations synthesized by nitric oxide synthases (NOS) present in cytoplasm of various cells. An additional Ca-dependent mitochondrial NOS (mtNOS) detected just recently synthesizes also NO inhibiting oxidative phosphorylation, i.e. mitochondrial energy producing metabolic process and protects mitochondria from oxygen radicals. Mitochondrial membrane possesses electrogenic uniporter transporting Ca into mitochondria (stimulation of mtNOS), while Na+/Ca2+ exchanger removes Ca from mitochondria. Mitochondrial disorders with low mtNOS activity participate in accelerated aging and age-related diseases. The direct NO balance determination is outside of the standard clinical facilities; Indirect alternatives, such as insulin resistance determination are accessible. Pharmacotherapy exploits effective therapeutic and preventive measures (NO donors, ACEI inhibitors, etc.) and pharmaceutical approach (development of mitochondriotropic drugs). We suggest, that mitochondrial disorders participate in aging and age related diseases and propose that the early diagnostics, preventive and therapeutic measures could prevent and even correct at least partially the development of age-related diseases (Tab. 4, Ref. 81).
Dzurik
R
R
Department of Clinical and Experimental Pharmacotherapy, Slovak Medical University, Bratislava, Slovakia.
Krivosikova
Z
Z
Stefikova
K
K
Spustova
V
V
D000368:Aged; D000375:Aging / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004734:Energy Metabolism; D006801:Humans; D024821:Metabolic Syndrome / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D051336:Mitochondrial Membranes / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism* / Q000502:physiology; D010085:Oxidative Phosphorylation
D004272:DNA, Mitochondrial; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase