Membrane potential generation coupled to oxidation of external NADH in liver mitochondria

Bodrova, M. E.; Dedukhova, V.I.; Mokhova, E. N.; Skulachev, Vladimir P.

doi:10.1016/s0014-5793(98)01072-2

Cited by 45 publications

(51 citation statements)

References 25 publications

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“…The propensity for electron slippage and free radical generation from the respiratory chain is enhanced with mitochondrial hyperpolarization, and the relief contributed by uncoupling of oxidative phosphorylation decreases ROS production (13,69,75,93,142). As would be predicted, inhibition of DLP1 function in experimental models of enhanced metabolic flux decreased ROS levels and oxidative stress across multiple tissue types, which was associated with respiration uncoupling (21,59,60,170).…”

Section: Progressive Changes Of Mitochondrial Energetics and Morpholomentioning

confidence: 69%

Mitochondrial Dynamics in Diabetic Cardiomyopathy

Galloway

Yoon

2015

Antioxidants & Redox Signaling

102

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Significance: Cardiac function is energetically demanding, reliant on efficient well-coupled mitochondria to generate adenosine triphosphate and fulfill the cardiac demand. Predictably then, mitochondrial dysfunction is associated with cardiac pathologies, often related to metabolic disease, most commonly diabetes. Diabetic cardiomyopathy (DCM), characterized by decreased left ventricular function, arises independently of coronary artery disease and atherosclerosis. Dysregulation of Ca 2+ handling, metabolic changes, and oxidative stress are observed in DCM, abnormalities reflected in alterations in mitochondrial energetics. Cardiac tissue from DCM patients also presents with altered mitochondrial morphology, suggesting a possible role of mitochondrial dynamics in its pathological progression. Recent Advances: Abnormal mitochondrial morphology is associated with pathologies across diverse tissues, suggesting that this highly regulated process is essential for proper cell maintenance and physiological homeostasis. Highly structured cardiac myofibers were hypothesized to limit alterations in mitochondrial morphology; however, recent work has identified morphological changes in cardiac tissue, specifically in DCM. Critical Issues: Mitochondrial dysfunction has been reported independently from observations of altered mitochondrial morphology in DCM. The temporal relationship and causative nature between functional and morphological changes of mitochondria in the establishment/progression of DCM is unclear. Future Directions: Altered mitochondrial energetics and morphology are not only causal for but also consequential to reactive oxygen species production, hence exacerbating oxidative damage through reciprocal amplification, which is integral to the progression of DCM. Therefore, targeting mitochondria for DCM will require better mechanistic characterization of morphological distortion and bioenergetic dysfunction. Antioxid. Redox Signal. 22, 1545Signal. 22, -1562

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Section: Progressive Changes Of Mitochondrial Energetics and Morpholomentioning

confidence: 69%

Mitochondrial Dynamics in Diabetic Cardiomyopathy

Galloway

Yoon

2015

Antioxidants & Redox Signaling

102

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“…This could in turn cause inefficient electron transport, resulting in the production of mitochondrial ROS. In support of this, mitochondria have been observed to have a DCm threshold, above which ROS are produced from the ETC (8,78). Increases in both b-oxidation (90,116) and ROS production from mitochondria have been reported to play a role in the development of oxidative stress conditions in NAFLD (64,106).…”

Section: Mitochondria In Nafldmentioning

confidence: 78%

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

118

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Significance: Mitochondria are the cellular energy-producing organelles and are at the crossroad of determining cell life and death. As such, the function of mitochondria has been intensely studied in metabolic disorders, including diabetes and associated maladies commonly grouped under all-inclusive pathological condition of metabolic syndrome. More recently, the altered metabolic profiles and function of mitochondria in these ailments have been correlated with their aberrant morphologies. This review describes an overview of mitochondrial fission and fusion machineries, and discusses implications of mitochondrial morphology and function in these metabolic maladies. Recent Advances: Mitochondria undergo frequent morphological changes, altering the mitochondrial network organization in response to environmental cues, termed mitochondrial dynamics. Mitochondrial fission and fusion mediate morphological plasticity of mitochondria and are controlled by membrane-remodeling mechanochemical enzymes and accessory proteins. Growing evidence suggests that mitochondrial dynamics play an important role in diabetes establishment and progression as well as associated ailments, including, but not limited to, metabolism-secretion coupling in the pancreas, nonalcoholic fatty liver disease progression, and diabetic cardiomyopathy. Critical Issues: While mitochondrial dynamics are intimately associated with mitochondrial bioenergetics, their cause-and-effect correlation remains undefined in metabolic diseases. Future Directions: The involvement of mitochondrial dynamics in metabolic diseases is in its relatively early stages. Elucidating the role of mitochondrial dynamics in pathological metabolic conditions will aid in defining the intricate form-function correlation of mitochondria in metabolic pathologies and should provide not only important clues to metabolic disease progression, but also new therapeutic targets. Antioxid. Redox Signal. 19,[415][416][417][418][419][420][421][422][423][424][425][426][427][428][429][430]

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“…This hypothesis is based upon the observation that mitochondrial membrane potential regulates the production of reactive oxygen species (ROS) (33)(34)(35)(36)(37). According to this hypothesis, mild mitochondrial uncoupling could markedly decrease superoxide production by decreasing the mitochondrial membrane potential below a critical level.…”

Section: Uncoupling Protein 3 (Ucp3)mentioning

confidence: 99%

“…According to this hypothesis, mild mitochondrial uncoupling could markedly decrease superoxide production by decreasing the mitochondrial membrane potential below a critical level. Thus, one of the functions of UCP3 could be to prevent the transmembrane electrochemical gradient from rising above a threshold critical for ROS formation (33,35).…”

Section: Uncoupling Protein 3 (Ucp3)mentioning

confidence: 99%

Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice

Vidal-Puig

Grujić

Zhang

et al. 2000

Journal of Biological Chemistry

628

553

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Uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily. Based upon its high homology with UCP1 and its restricted tissue distribution to skeletal muscle and brown adipose tissue, UCP3 has been suggested to play important roles in regulating energy expenditure, body weight, and thermoregulation. Other postulated roles for UCP3 include regulation of fatty acid metabolism, adaptive responses to acute exercise and starvation, and prevention of reactive oxygen species (ROS) formation. To address these questions, we have generated mice lacking UCP3 (UCP3 knockout (KO) mice). Here, we provide evidence that skeletal muscle mitochondria lacking UCP3 are more coupled (i.e. increased state 3/state 4 ratio), indicating that UCP3 has uncoupling activity. In addition, production of ROS is increased in mitochondria lacking UCP3. This study demonstrates that UCP3 has uncoupling activity and that its absence may lead to increased production of ROS. Despite these effects on mitochondrial function, UCP3 does not seem to be required for body weight regulation, exercise tolerance, fatty acid oxidation, or cold-induced thermogenesis. The absence of such phenotypes in UCP3 KO mice could not be attributed to up-regulation of other UCP mRNAs. However, alternative compensatory mechanisms cannot be excluded. The consequence of increased mitochondrial coupling in UCP3 KO mice on metabolism and the possible role of yet unidentified compensatory mechanisms, remains to be determined. Uncoupling protein 3 (UCP3)1 (1-3) is a member of the mitochondrial anion carrier superfamily with high homology (57%) to UCP1, a well characterized uncoupling protein (4, 5). UCP3 together with UCP1, UCP2 (6, 7), and possibly BMCP1 (brain mitochondrial carrier protein) (8) and UCP4 (9), form a family of uncoupling proteins located in the inner mitochondrial membrane. The evidence supporting the uncoupling activity of these proteins comes from studies where UCPs have been heterologously expressed in yeast or reconstituted into proteoliposomes. The expression of UCP2 and -3 decreases the mitochondrial membrane potential, as assessed by uptake of fluorescent membrane potential-sensitive dyes in whole yeast. They also increase state 4 respiration in isolated mitochondria, which serves as an indicator of inner membrane proton leak (3, 6, 10). More recently, reconstitution of UCPs into liposomes has shown that UCP2 and UCP3, like UCP1, mediate proton transport across bilipid layers (11). It is well established that UCP1 is exclusively expressed in brown fat, where it plays a key role in facultative thermogenesis in rodents. Although there is controversy about the molecular mechanisms involved (12-16), it is clear that activated UCP1 catalyzes a proton leak across the mitochondrial inner membrane leading to thermogenesis. The activity of UCP1 is highly regulated, facilitated by fatty acids and inhibited by purine ribose di-and trinucleotides (ATP, ADP, GTP, GDP) (17). UCP1 is also highly regulated at the transcriptional level (18) by cat...

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Membrane potential generation coupled to oxidation of external NADH in liver mitochondria

Cited by 45 publications

References 25 publications

Mitochondrial Dynamics in Diabetic Cardiomyopathy

Mitochondrial Dynamics in Diabetic Cardiomyopathy

Mitochondrial Morphology in Metabolic Diseases

Energy Metabolism in Uncoupling Protein 3 Gene Knockout Mice

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