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Age-associated decline in mitochondrial respiration and electron transport in Drosophila melanogaster.

ABSTRACT: The principal objective of the present study was to identify specific alterations in mitochondrial respiratory functions during the aging process. Respiration rates and the activities of electron transport chain complexes were measured at various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila melanogaster, which consist primarily of flight muscles. The rates of state 3 respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled respiration rates decreased significantly as a function of age, using either NAD+- or FAD-linked substrates; however, there were no differences in state 4 respiration (ADP-depleted) rates. There was also a significant age-related decline in the activity of cytochrome c oxidase (complex IV), but not of the other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated from young flies to low doses of KCN or NaAz (sodium azide), complex IV inhibitors, decreased cytochrome c oxidase activity and increased the production of H2O2. Collectively, these results support the hypothesis that impairment of mitochondrial respiration may be a causal factor in the aging process, and that such impairment may result from and contribute to increased H2O2 production in vivo.

SUBMITTER: Ferguson M

PROVIDER: S-EPMC1198930 | biostudies-other | 2005 Sep

REPOSITORIES: biostudies-other

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Genes expressed in age-induced mitochondrial DNA deletion mutation containing / Electron Transport abnormal cells

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Genes expressed in age-induced mitochondrial DNA deletion mutation containing / Electron Transport abnormal cells

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Project description:The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, and its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of NLRP3 inflammasome through multiple mechanisms including generation of mitochondrial ROS. Here we report that mitochondrial electron transport chain (ETC) complexes I, II, III and V inhibitors all prevent NLRP3 inflammasome activation. Ectopic expression of Saccharomyces cerevisiae NADH dehydrogenase (NDI1) or Ciona intestinalis alternative oxidase (AOX), which can respectively complement the functional loss of mitochondrial complex I or III, without generation of ROS, rescued NLRP3 inflammasome activation in the absence of endogenous mitochondrial complex I or complex III function. Metabolomics revealed phosphocreatine (PCr), which can sustain ATP levels, as a common metabolite that is diminished by mitochondrial ETC inhibitors. PCr depletion decreased ATP levels and NLRP3 inflammasome activation. Thus, mitochondrial ETC sustains NLRP3 inflammasome activation through PCr-dependent generation of ATP but a ROS independent mechanism.

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Inhibition of the mitochondrial electron transport chain by antimycin A in Arabidopsis thaliana

Project description:Plant mitochondria signal to the nucleus leading to altered transcription of nuclear genes by a process called mitochondrial retrograde regulation (MRR). MRR is implicated in metabolic homeostasis and responses to stress conditions. Transcriptional consequences on nuclear gene expression of mitochondrial perturbations were examined by a microarray analyses. Expression of 1316 was altered by antimycin A (AA) inhibition of the cytochrome respiratory pathway in leaves of soil grown Arabidopsis plants in the dark for 6 hours. Functional gene category (MapMan) and cluster analyses showed that genes with expression levels affected by perturbation from AA or MFA inhibition were most similarly affected by biotic stresses such as pathogens, not oxidative stresses. Overall, the data provide further evidence for the presence of mtROS-independent MRR signaling, and support the proposed involvement of MRR and mitochondrial function in plant responses to biotic stress. Three independent (bio-replicate) experiments were done using three independent plant samples and independent chemicals in the treatments. For each, approximately 30 plants were used for the treated sample and about 30 plants were used as the control treated sample. Plants were treated with 20 uM antimycin A in 0.01% Tween 20 and incubated in the dark at room temperature (25C) for 6 hours. RNA was isolated from the inhibitor treated and control treated plants and used for microarray experiments. For each independent (bio-replicate) experiment, two microarrays were utilized using Cy3 and Cy5 dye-labeled samples and dye swapping was incorporated- so, minimum of 2 microarrays for each of 3 independent experiments (6 microarrays). In addition, two of the microarrays were duplicated so that a total of 8 slides were used in the data analyses.

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