Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria

Hensley, Kenneth; Kotake, Yashige; Sang, Hong; Pye, Quentin N.; Wallis, Gemma; Kolker, Lisa M.; Tabatabaie, Tahereh; Stewart, Charles A.; Konishi, Yoichi; Nakae, Dai; Floyd, Robert A.

doi:10.1093/carcin/21.5.983

Cited by 164 publications

(113 citation statements)

References 27 publications

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“…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). Enhanced cellular ROS are thought to act in close proximity to their production and oxidize proteins, lipids, and DNA, thereby altering their ascribed function or rendering them nonfunctional.…”

Section: Mitochondria In Nafldmentioning

confidence: 88%

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

111

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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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Section: Mitochondria In Nafldmentioning

confidence: 88%

Mitochondrial Morphology in Metabolic Diseases

Galloway

Yoon

2013

Antioxidants & Redox Signaling

111

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“…If electron flow is interrupted at any point in the respirator y chain, the preceding respirator y intermediates can transfer electrons to molecular oxygen to produce superoxide anions and hydrogen peroxide [40,41] . Malondialdehyde and 4-hydroxynonenal, two byproducts of lipid peroxidation, can inhibit mitochondrial cytochrome c oxidase by for ming adducts with this enzyme.…”

Section: Mitochondrial Dysfunction In Nafldmentioning

confidence: 99%

Nonalcoholic fatty liver disease and mitochondrial dysfunction

Wei¹,

Rector²,

Thyfault³

et al. 2008

WJG

296

254

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Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

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“…1). Rotenone, an inhibitor of mitochondrial complex I, was used to produce ROS, which originated from the mitochondria, because impaired electrons transfer at complex I has been reported to be associated with an increased production of superoxide radicals (Hensley et al, 2000). Rotenone induced a significant increase in the oxidation level of DHE, a widely used ROS-sensitive dye (Fig.…”

Section: Inhibitory Effect Of Tfam Overexpression On Rotenoneinduced mentioning

confidence: 99%

Reverse of Age-Dependent Memory Impairment and Mitochondrial DNA Damage in Microglia by an Overexpression of Human Mitochondrial Transcription Factor A in Mice

et al. 2008

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Mitochondrial DNA (mtDNA) is highly susceptible to injury induced by reactive oxygen species (ROS). During aging, mutations of mtDNA accumulate to induce dysfunction of the respiratory chain, resulting in the enhanced ROS production. Therefore, age-dependent memory impairment may result from oxidative stress derived from the respiratory chain. Mitochondrial transcription factor A (TFAM) is now known to have roles not only in the replication of mtDNA but also its maintenance. We herein report that an overexpression of TFAM in HeLa cells significantly inhibited rotenone-induced mitochondrial ROS generation and the subsequent NF-B (nuclear factor-B) nuclear translocation. Furthermore, TFAM transgenic (TG) mice exhibited a prominent amelioration of an age-dependent accumulation of lipid peroxidation products and a decline in the activities of complexes I and IV in the brain. In the aged TG mice, deficits of the motor learning memory, the working memory, and the hippocampal long-term potentiation (LTP) were also significantly improved. The expression level of interleukin-1␤ (IL-1␤) and mtDNA damages, which were predominantly found in microglia, significantly decreased in the aged TG mice. The IL-1␤ amount markedly increased in the brain of the TG mice after treatment with lipopolysaccharide (LPS), whereas its mean amount was significantly lower than that of the LPS-treated aged wild-type mice. At the same time, an increased mtDNA damage in microglia and an impaired hippocampal LTP were also observed in the LPS-treated aged TG mice. Together, an overexpression of TFAM is therefore considered to ameliorate age-dependent impairment of the brain functions through the prevention of oxidative stress and mitochondrial dysfunctions in microglia.

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Dietary choline restriction causes complex I dysfunction and increased H2O2 generation in liver mitochondria

Cited by 164 publications

References 27 publications

Mitochondrial Morphology in Metabolic Diseases

Mitochondrial Morphology in Metabolic Diseases

Nonalcoholic fatty liver disease and mitochondrial dysfunction

Reverse of Age-Dependent Memory Impairment and Mitochondrial DNA Damage in Microglia by an Overexpression of Human Mitochondrial Transcription Factor A in Mice

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