Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology

Giulivi, Cecilia R; Kato, Kazunobu; Cooper, Chris E.

doi:10.1152/ajpcell.00307.2006

Cited by 109 publications

(99 citation statements)

References 104 publications

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“…Under physiological conditions, the production of NO by mitochondria has been shown to be important for maintenance of the cellular metabolism, i.e. it modulates oxygen consumption (17,21,36). The decrease in NO production by uncoupling of mitochondrial NOS may lead to mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload

Shimizu

Ishibashi

Kumagai

et al. 2013

International Journal of Molecular Medicine

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Abstract. Sustained cardiac pressure overload induces mitochondrial dysfunction and apoptosis of cardiomyocytes leading to pathological cardiac hypertrophy and dysfunction. Mitochondrial nitric oxide synthase (NOS) appears to cause uncoupling, which produces reactive oxygen species (ROS) instead of nitric oxide (NO), by a decrease in the cofactor tetrahydrobiopterin (BH4). This study focused on examining the changes in mitochondrial BH4 levels during cardiac pressure overload. Chronic cardiac pressure overload was generated by abdominal aortic banding in rats. Levels of BH4 and its oxidized form were measured in the mitochondria isolated from the left ventricle (LV) and the post-mitochondrial supernatants. Chronic aortic banding increased blood pressure, and induced cardiac hypertrophy and fibrosis. Notably, the BH4 levels were decreased while its oxidized forms were increased in LV mitochondria, but not in the post-mitochondrial supernatants containing the cytosol and microsome. Anti-neuronal NOS antibody-sensitive protein was detected in the cardiac mitochondria. Moreover, continuous administration of BH4 to rats with pressure overload increased mitochondrial BH4 levels and reduced cardiac fibrosis and matrix metallopeptidase activity, but not cardiac hypertrophy. These findings show the possibility that NOS uncoupling by decreased cardiac mitochondrial BH4 levels is implicated, at least in part, in the development of cardiac fibrosis, leading to cardiac dysfunction induced by pressure overload.

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Section: Discussionmentioning

confidence: 99%

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload

Shimizu

Ishibashi

Kumagai

et al. 2013

International Journal of Molecular Medicine

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“…All aerobic organisms require oxygen for oxidative phosphorylation, and the mitochondria are central organelles that generate a number of cellular oxidants. 65 Moreover, nitric oxide regulates oxygen consumption, metabolism, and ROS production in the mitochondria 66 and can be generated through NOS-dependent and -independent pathways. 67 One of the most common ROS generated by the mitochondria is superoxide (O 2…”

Section: Generation Of Ros and Rns In Cells And Antioxidant Defensementioning

confidence: 99%

Rho GTPases, oxidation, and cell redox control

et al. 2014

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“…NO regulates mitochondrial function by providing a tonic inhibitory control on the oxidative phosphorylation (5,7,11). This modulation of oxygen consumption prevents excess O 2 Ϫ formation, thus decreasing reactive oxygen species (ROS)-induced cell damage (3,18).…”

mentioning

confidence: 99%

Nitrotyrosine impairs mitochondrial function in fetal lamb pulmonary artery endothelial cells

Teng

Afolayan

et al. 2016

American Journal of Physiology-Cell Physiology

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Teng RJ, Wu TJ, Afolayan AJ, Konduri GG. Nitrotyrosine impairs mitochondrial function in fetal lamb pulmonary artery endothelial cells. Am J Physiol Cell Physiol 310: C80 -C88, 2016. First published October 21, 2015 doi:10.1152/ajpcell.00073.2015.-Nitration of both protein-bound and free tyrosine by reactive nitrogen species results in the formation of nitrotyrosine (NT). We previously reported that free NT impairs microtubule polymerization and uncouples endothelial nitric oxide synthase (eNOS) function in pulmonary artery endothelial cells (PAEC). Because microtubules modulate mitochondrial function, we hypothesized that increased NT levels during inflammation and oxidative stress will lead to mitochondrial dysfunction in PAEC. PAEC isolated from fetal lambs were exposed to varying concentrations of free NT. At low concentrations (1-10 M), NT increased nitration of mitochondrial electron transport chain (ETC) protein subunit complexes I-V and state III oxygen consumption. Higher concentrations of NT (50 M) caused decreased microtubule acetylation, impaired eNOS interactions with mitochondria, and decreased ETC protein levels. We also observed increases in heat shock protein-90 nitration, mitochondrial superoxide formation, and fragmentation of mitochondria in PAEC. Our data suggest that free NT accumulation may impair microtubule polymerization and exacerbate reactive oxygen species-induced cell damage by causing mitochondrial dysfunction. ) is formed as a byproduct during oxidative phosphorylation, from mitochondrial complexes I and III electron leakage (3). Increased mitochondrial O 2 Ϫ generation is a major contributor to oxidative stress in cells, and the adaptive mechanisms that decrease mitochondrial O 2 Ϫ levels, including manganese superoxide dismutase (MnSOD), are critical to cell survival. Recent studies provided evidence that nitric oxide (NO) may affect mitochondrial O 2 Ϫ formation by modulating oxidative phosphorylation (40) and mitochondrial biogenesis (37). This interaction is believed to play a critical role in vasomotor control.Gao et al. demonstrated that disrupting endothelial nitric oxide synthase (eNOS) association with mitochondrial outer membrane leads to an increase in mitochondrial oxygen consumption in endothelial cells (17). NO regulates mitochondrial function by providing a tonic inhibitory control on the oxidative phosphorylation (5,7,11). This modulation of oxygen consumption prevents excess O 2 Ϫ formation, thus decreasing reactive oxygen species (ROS)-induced cell damage (3, 18).Intimate association between mitochondria and microtubules has been described for more than 30 years (21). Microtubules interact with voltage-dependent anion channel (porin) of mitochondrial outer membrane (10) to regulate mitochondrial function (41). Agents that disturb microtubule polymerization can affect mitochondrial biogenesis (24) and mitochondrial ROS formation (51). It is likely that microtubule-active agents can disturb eNOS-mitochondrial interaction.We previously reported that free nitrotyro...

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Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology

Cited by 109 publications

References 104 publications

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload

Rho GTPases, oxidation, and cell redox control

Nitrotyrosine impairs mitochondrial function in fetal lamb pulmonary artery endothelial cells

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