Mitochondrial encephalomyopathy and lactic acidosis with strokelike episodes (MELAS) is a severe young onset stroke disorder without effective treatment. We have identified a MELAS patient harboring a 13528A3 G mitochondrial DNA (mtDNA) mutation in the Complex I ND5 gene. This mutation was homoplasmic in mtDNA from patient muscle and nearly homoplasmic (99.9%) in blood. Fibroblasts from the patient exhibited decreased mitochondrial membrane potential (⌬ m ) and increased lactate production, consistent with impaired mitochondrial function. Transfer of patient mtDNA to a new nuclear background using transmitochondrial cybrid fusions confirmed the pathogenicity of the 13528A3 G mutation; Complex I-linked respiration and ⌬ m were both significantly reduced in patient mtDNA cybrids compared with controls. Inhibition of the adenine nucleotide translocase or the F 1 F 0 -ATPase with bongkrekic acid or oligomycin caused a loss of potential in patient mtDNA cybrid mitochondria, indicating a requirement for glycolytically generated ATP to maintain ⌬ m . This was confirmed by inhibition of glycolysis with 2-deoxy-Dglucose, which caused depletion of ATP and mitochondrial depolarization in patient mtDNA cybrids. These data suggest that in response to impaired respiration due to the mtDNA mutation, mitochondria consume ATP to maintain ⌬ m , representing a potential pathophysiological mechanism in human mitochondrial disease.Mitochondrial respiration is fundamental to the well being of most mammalian cells, since it provides the central mechanism that couples fuel and oxygen consumption to ATP synthesis. The mitochondrial respiratory chain resides at the inner membrane and consists of five multimeric enzyme complexes: I (NADH:ubiquinone oxidoreductase), II (succinate:ubiquinone oxidoreductase), III (ubiquinol:cytochrome c oxidoreductase), IV (cytochrome c oxidase), and V (F 1 F 0 -ATPase). Electrons donated from the tricarboxylic acid cycle to Complexes I and II are utilized by Complexes I, III, and IV to pump protons from the matrix to the intermembrane space. The resulting electrochemical potential gradient, normally expressed as a mitochondrial membrane potential (⌬ m ), 2 provides the energy to drive ATP synthesis by Complex V (1, 2).Mitochondria contain their own unique, double-stranded, circular genome, which encodes the 13 essential protein subunits of the respiratory complexes. It also encodes the 12 and 16 S rRNAs and the 22 tRNAs specific for mitochondrial protein synthesis. Mutations in mitochondrial DNA (mtDNA) are associated with a wide variety of multisystemic degenerative diseases (3). Aspects of central nervous system and muscle function are usually affected, whereas a number of mutations are also variably associated with deafness, diabetes, and optic nerve atrophy or retinal degeneration (2, 4). In many cases, the pathogenic mtDNA mutation associated with the respiratory defect has been assigned, but it is still unclear why different mtDNA mutations result in such a wide array of clinical phenotypes.Mitochondr...

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Chitosan-based biologicals and chemicals have been proved to possess antiviral, antibacterial and antimycotic activity, and be able to stimulate plant immunity. In field trials (Tashkent region, Uzbekistan, 2015-2016) we first evaluated an impact of seed encapsulation with UzChitan, chitosan ascorbate and Cu 2+-chelating chitosan synthesized by the authors' method in the Institute of Chemistry and Polymer Physics of the National University of Uzbekistan (NUUz, Tashkent) from waste of silkworm cocoon processing on photosynthetic activity at wilt (Verticillium dahliae) artificial infection and in wilt-free (healthy) crops of cotton (Gossypium L., 1753) variety Sultan. It was found that wilt-affected control plants (non-treated with chitosan derivatives) had higher specific leaf weight (SLW index), their chlorophyll content was reduced and rates of respiration and apparent photosynthesis were depressed in comparison with healthy control plants. Chlorophyll content in infected control plants was decreased by 27-30 % in terms of mg/g. Meanwhile, all plants from pretreated seeds contained more chlorophyll compared to control: the pigment content (mg/g of dry matter) was 25.5 and 17.7 % higher when ascorbate and Cu 2+-chelating chitosan used. Chlorophyll content in leaves did not vary significantly in absence of the pathogen. The apparent photosynthesis rate in control under wilt was reduced by 33 % (0.161±0.027 against 0.245±0.028 mol O 2 Ÿm  2 Ÿsec  1). That corresponds to toxic effect of pathogen which penetrates through roots and goes up into top parts of plants, damages their phloem system, disturbs water transport, and destroys chlorophyll and leaf tissues. Besides, some tendency to respiration rate inhibition was observed for non-treated cotton plants under wilt infection (by 22 % compared to control plants from the healthy field). Net-oxygen production (apparent photosynthesis) rates in the treated groups were higher as compared to control plants under wilt; the best results were shown by ascorbate and Cu 2+-chelating chitosan (54 and 46 % higher, respectively). Respiration rates did not differ significantly in all groups under wilt. Oxygen balance (OB) index, estimated as ratio between measured oxygen net-production and oxygen consumption rates, which reflects physiological status of plants under biogenic stress (including pathogen fungi), did not change significantly in a healthy environment when chitosan derivatives used. Under wilt, the plants from pre-treated seeds possessed higher OB indices than the corresponding control plant from the same field. Thus, the OB values with ascorbate and Cu 2+-chelating chitosan were higher compared to control by 36 and 52 %, respectively. Our findings indicate that in case the cotton seeds were pre-treated with chitosan derivatives, the oxygen production, oxygen consumption and OB indices were not significantly different in the pathogen-affected and unaffected plants. Thus we can conclude about a nonspecific resistance of cotton plants to wilt (Verticillium dahliae) ind...

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