Effect of anoxia/reperfusion on the reversible active/de-active transition of NADH–ubiquinone oxidoreductase (complex I) in rat heart

Maklashina, Elena; Sher, Yelizaveta; Zhou, Hui-Zhong; Gray, Mary O.; Karliner, Joel S.; Cecchini, Gary

doi:10.1016/s0005-2728(02)00280-3

Cited by 71 publications

(58 citation statements)

References 33 publications

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“…Prolonged air exposure resulted in a reduced maximum capacity of mitochondrial ETC in oysters (as indicated by a significant decline in the rate of uncoupled mitochondrial respiration by 17-25%). This finding agrees with earlier studies in mammalian models showing inhibitory effects of oxygen deficiency on activity of ETC complexes (including complexes I, II, and III) and matrix enzymes such as aconitase (32,45,55). In oysters, the anoxiainduced decrease in ETC capacity had no dramatic impact on ADP-stimulated or resting respiration rates during anoxia/ reoxygenation.…”

Section: Discussionsupporting

confidence: 92%

Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica)

Kurochkin

Ivanina

Eilers

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Kurochkin IO, Ivanina AV, Eilers S, Downs CA, May LA, Sokolova IM. Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica). Am J Physiol Regul Integr Comp Physiol 297: R1262-R1272, 2009. First published September 2, 2009 doi:10.1152/ajpregu.00324.2009.-Benthic marine organisms such as mollusks are often exposed to periodic oxygen deficiency (due to the tidal exposure and/or seasonal expansion of the oxygen-deficient dead zones) and pollution by metals [e.g., cadmium, (Cd)]. These stressors can strongly affect mollusks' survival; however, physiological mechanisms of their combined effects are not fully understood. We studied the effects of Cd exposure on metabolic responses to prolonged anoxia and subsequent recovery in anoxia-tolerant intertidal mollusks Crassostrea virginica (eastern oysters). Anoxia led to an onset of anaerobiosis indicated by accumulation of L-alanine, acetate, and succinate. Prolonged anoxia (for 6 days) caused a decline in the maximum activity of electron transport chain and ADP-stimulated (state 3) oxygen uptake by mitochondria (MO 2), but no change in the resting (state 4) MO 2 of oyster mitochondria, along with a slight but significant reduction of mitochondrial respiratory control ratio. During reoxygenation, there was a significant overshoot of mitochondrial MO 2 (by up to 70% above the normoxic steady-state values) in control oysters. Mild mitochondrial uncoupling during prolonged shutdown in anoxic tissues and a subsequent strong stimulation of mitochondrial flux during recovery may help to rapidly restore redox status and protect against elevated reactive oxygen species formation in oysters. Exposure to Cd inhibits anaerobic metabolism, abolishes reoxygenation-induced stimulation of mitochondrial MO 2, and leads to oxidative stress (indicated by accumulation of DNA lesions) and a loss of mitochondrial capacity during postanoxic recovery. This may result in increased sensitivity to intermittent hypoxia and anoxia in Cd-exposed mollusks and will have implications for their survival in polluted estuaries and coastal zones. air exposure; recovery; mitochondrial function; oxidative damage; mollusks PERIODICAL OXYGEN DEFICIENCY is an important environmental stressor in intertidal and coastal habitats. Short-term intermittent hypoxia/anoxia (from several hours to several days, depending on the state of the tides) often occurs in intertidal invertebrates during the low tide, and may also occur in tidal pools and shallow lagoons with limited water exchange (8,36,49). Furthermore, long-term severe hypoxia and anoxia triggered by anthropogenic release of nutrients has become a serious issue in many estuaries and coastal zones rivaling the climate change (18,22). In the coastal dead zones, benthic invertebrates including mollusks can be exposed to severe hypoxia or anoxia for prolonged periods (from weeks to up to several months) (10,22,34,46). Long-term oxygen deficiency often leads to the massive die-offs in species with limited or...

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Section: Discussionsupporting

confidence: 92%

Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica)

Kurochkin

Ivanina

Eilers

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The accumulation of succinate in tissues during hypoxia and the reprogramming of respiratory enzyme performance develop fast and under different levels of oxygenation. For example, Goldberg et al, found that after 30 sec of global brain ischemia, succinate level increased 1.5 times in the setting of reduced concentrations of certain NAD-dependent substrates [19]. Similar data were also obtained by other researchers.…”

Section: Performance Of Respiratory Chain In Hypoxiasupporting

confidence: 66%

“…This process is associated with activation of MtC II (SDH) and increased contribution of succinate oxidation to cell respiration; this contribution may reach 70% -80% [4,[6][7][8][9][10][11][16][17][18][19]21,22,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41].…”

Section: Performance Of Respiratory Chain In Hypoxiamentioning

confidence: 99%

Mitochondrial Signaling in Hypoxia

Luk’yanova¹

2013

OJEMD

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This paper focuses on a bioenergetic mechanism responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory chain function and switching from oxidation of complex I (NAD-related substrates) to complex II (succinate oxidation). Transient, reversible, compensatory activation of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia, which is necessary for 1) succinate-related energy synthesis in the conditions of oxygen shortage and formation of urgent resistance; 2) succinate-related stabilization of HIF-1α and initiation of its transcriptional activity related with formation of long-term adaptation; 3) succinate-dependent activation of the succinate-specific receptor GPR91. Thus, mitochondria perform a signaling function with succinate as a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular and intercellular. In these settings, succinate displays antihypoxic activity. The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants with energotropic properties.

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“…Interestingly, the sensitivity of complex I to zinc probably increases under these conditions, when the enzyme is not fully catalytically active. Note that the existence of the deactive state remains to be demonstrated in vivo but that it has been reported in studies of anoxia using rat hearts (47) and in isolated mitochondria (44). Finally, comparison of the IC 50 values determined here with the zinc binding constants determined for the cytochrome bc 1 complex (0.…”

Section: Is Complex I Inhibition Relevant To Zn 2ϩmentioning

confidence: 67%

The Inhibition of Mitochondrial Complex I (NADH:Ubiquinone Oxidoreductase) by Zn2+

Sharpley

Hirst

2006

Journal of Biological Chemistry

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NADH:ubiquinone oxidoreductase (complex I) from bovine heart mitochondria is a highly complicated, membrane-bound enzyme. It is central to energy transduction, an important source of cellular reactive oxygen species, and its dysfunction is implicated in neurodegenerative and muscular diseases and in aging. Here, we describe the effects of Zn 2؉ on complex I to define whether complex I may contribute to mediating the pathological effects of zinc in states such as ischemia and to determine how Zn 2؉ can be used to probe the mechanism of complex I. Zn 2؉ inhibits complex I more strongly than Mg 2؉ , Ca 2؉ , Ba 2؉ , and Mn 2؉ to Cu 2؉ or Cd 2؉ . It does not inhibit NADH oxidation or intramolecular electron transfer, so it probably inhibits either proton transfer to bound quinone or proton translocation. Thus, zinc represents a new class of complex I inhibitor clearly distinct from the many ubiquinone site inhibitors. No evidence for increased superoxide production by zinc-inhibited complex I was detected. Zinc binding to complex I is mechanistically complicated. During catalysis, zinc binds slowly and progressively, but it binds rapidly and tightly to the resting state(s) of the enzyme. Reactivation of the inhibited enzyme upon the addition of EDTA is slow, and inhibition is only partially reversible. The IC 50 value for the Zn 2؉ inhibition of complex I is high (10 -50 M, depending on the enzyme state); therefore, complex I is unlikely to be a major site for zinc inhibition of the electron transport chain. However, the slow response of complex I to a change in Zn 2؉ concentration may enhance any physiological consequences.

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Effect of anoxia/reperfusion on the reversible active/de-active transition of NADH–ubiquinone oxidoreductase (complex I) in rat heart

Cited by 71 publications

References 33 publications

Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica)

Cadmium affects metabolic responses to prolonged anoxia and reoxygenation in eastern oysters (Crassostrea virginica)

Mitochondrial Signaling in Hypoxia

The Inhibition of Mitochondrial Complex I (NADH:Ubiquinone Oxidoreductase) by Zn2+

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