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Journal ArticleDOI

Mitochondrial dysfunction and molecular pathways of disease.

01 Aug 2007-Experimental and Molecular Pathology (Exp Mol Pathol)-Vol. 83, Iss: 1, pp 84-92
TL;DR: Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat mitochondrial diseases and dysfunction, and antioxidant therapies hold promise for improving mitochondrial performance.
About: This article is published in Experimental and Molecular Pathology.The article was published on 2007-08-01. It has received 564 citations till now. The article focuses on the topics: Mitochondrion & Dementia.
Citations
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Journal ArticleDOI
TL;DR: Overall, this review outlines various mechanisms that lead to the development of oxidative stress and intervention and therapy that alter or disrupt these mechanisms may serve to reduce the risk of insulin resistance and theDevelopment of diabetes.

1,125 citations


Cites background from "Mitochondrial dysfunction and molec..."

  • ...Mitochondria are the main power supply for our cells and play a central role in cell life and death [50,51]....

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Journal ArticleDOI
TL;DR: Myalgic encephalomyelitis: International Consensus Criteria (Review).
Abstract: 12 FatigueConsultationClinic,SaltLake RegionalMedicalCenter; 13 InternalMedicine,FamilyPractice,UniversityofUtah,SaltLakeCity,UT,USA; 14 ME ⁄CFSCenter,OsloUniversity HospitalHF,Norway; 15 DepartmentofPaediatrics,StateUniversityofNewYork,Buffalo,NY,USA; 16 Independent,Pavia,Italy; 17 Harbor-UCLA MedicalCenter,UniversityofCalifornia,LosAngeles,CA; 18 EVMedResearch,Lomita,CA,USA; 19 UniversityofLimerick,Limerick,Ireland; 20 Pain Clinic,KonyangUniversityHospital,Daejeon,Korea; 21 DonvaleSpecialistMedicalCentre,Donvale,Victoria,Australia; 22 Departmentsof Anesthesiology,NeurobiologyandAnatomy,UniversityofUtah,SaltLakeCity,UT,USA; 23 DepartmentofMedicinaNuclear,ClinicaLasCondes, Santiago,Chile; 24 WhittemorePetersonInstitute,UniversityofNevada,Reno,NV,USA; 25 MiwaNaikaClinic,Toyama,Japan; 26 A.Kirchenstein InstituteofMicrobiologyandVirology,RigaStradinsUniversity,Riga,Latvia; 27 DepartmentofBiochemistryBand 28 DepartmentofSportsSciences,UniversityofthePacific,Stockton,CAUSA

810 citations


Cites background from "Mitochondrial dysfunction and molec..."

  • ...Myalgic encephalomyelitis (ME), also referred to in the literature as chronic fatigue syndrome (CFS), is a complex disease involving profound dysregulation of the central nervous system (CNS) [1-3] and immune system [4-8], dysfunction of cellular energy metabolism and ion transport [9-11], and cardiovascular abnormalities [12-14]....

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Journal ArticleDOI
TL;DR: The purpose of the article is to highlight the recent progress on the mitochondrial role in metabolic syndromes and also summarize the progress of mitochondria-targeted molecules as therapeutic targets to treat metabolic Syndromes.

724 citations


Cites background from "Mitochondrial dysfunction and molec..."

  • ...Mitochondrial dysfunction is defined as diminished mitochondrial biogenesis, altered membrane potential, and the decrease in mitochondrial number and altered activities of oxidative proteins due to the accumulation of ROS in cells and tissues [89]....

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Journal ArticleDOI
TL;DR: Statin administration is accompanied by risk reduction in all major vascular events in patients with CKD that are considered high-risk patients, and beneficial effects seem to be consequence of not only their hypolipidemic effect but especially their pleitropic actions that involve modulation of oxidative stress and inflammation.

529 citations

Journal ArticleDOI
15 Aug 2008-Blood
TL;DR: It is demonstrated that Ulk1, a serine threonine kinase with homology to yeast atg1p, is a critical regulator of mitochondrial and ribosomal clearance during the final stages of erythroid maturation, and that expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice.

528 citations

References
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Journal ArticleDOI
TL;DR: It is argued that this damage to DNA, protein, and lipid is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts.
Abstract: Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.

6,007 citations

Journal ArticleDOI

5,682 citations


"Mitochondrial dysfunction and molec..." refers background in this paper

  • ...Mitochondria produce more than 90% of our cellular energy by ox-phos (Chance et al., 1979)....

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Journal ArticleDOI
11 Sep 2003-Neuron
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.

4,872 citations


"Mitochondrial dysfunction and molec..." refers background in this paper

  • ...Complex I is especially susceptible to nitric oxide (NO) damage, and animals administered natural and synthetic complex I antagonists have undergone death of neurons (Dauer and Przedborski, 2003; Betarbet et al., 2000; Qi et al., 2003)....

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Journal ArticleDOI
TL;DR: This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.
Abstract: Metal-induced toxicity and carcinogenicity, with an emphasis on the generation and role of reactive oxygen and nitrogen species, is reviewed. Metal-mediated formation of free radicals causes various modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulfhydryl homeostasis. Lipid peroxides, formed by the attack of radicals on polyunsaturated fatty acid residues of phospholipids, can further react with redox metals finally producing mutagenic and carcinogenic malondialdehyde, 4-hydroxynonenal and other exocyclic DNA adducts (etheno and/or propano adducts). Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins. Arsenic (As) is thought to bind directly to critical thiols, however, other mechanisms, involving formation of hydrogen peroxide under physiological conditions, have been proposed. The unifying factor in determining toxicity and carcinogenicity for all these metals is the generation of reactive oxygen and nitrogen species. Common mechanisms involving the Fenton reaction, generation of the superoxide radical and the hydroxyl radical appear to be involved for iron, copper, chromium, vanadium and cobalt primarily associated with mitochondria, microsomes and peroxisomes. However, a recent discovery that the upper limit of "free pools" of copper is far less than a single atom per cell casts serious doubt on the in vivo role of copper in Fenton-like generation of free radicals. Nitric oxide (NO) seems to be involved in arsenite-induced DNA damage and pyrimidine excision inhibition. Various studies have confirmed that metals activate signalling pathways and the carcinogenic effect of metals has been related to activation of mainly redox-sensitive transcription factors, involving NF-kappaB, AP-1 and p53. Antioxidants (both enzymatic and non-enzymatic) provide protection against deleterious metal-mediated free radical attacks. Vitamin E and melatonin can prevent the majority of metal-mediated (iron, copper, cadmium) damage both in vitro systems and in metal-loaded animals. Toxicity studies involving chromium have shown that the protective effect of vitamin E against lipid peroxidation may be associated rather with the level of non-enzymatic antioxidants than the activity of enzymatic antioxidants. However, a very recent epidemiological study has shown that a daily intake of vitamin E of more than 400 IU increases the risk of death and should be avoided. While previous studies have proposed a deleterious pro-oxidant effect of vitamin C (ascorbate) in the presence of iron (or copper), recent results have shown that even in the presence of redox-active iron (or copper) and hydrogen peroxide, ascorbate acts as an antioxidant that prevents lipid peroxidation and does not promote protein oxidation in humans in vitro. Experimental results have also shown a link between vanadium and oxidative stress in the etiology of diabetes. The impact of zinc (Zn) on the immune system, the ability of zinc to act as an antioxidant in order to reduce oxidative stress and the neuroprotective and neurodegenerative role of zinc (and copper) in the etiology of Alzheimer's disease is also discussed. This review summarizes recent findings in the metal-induced formation of free radicals and the role of oxidative stress in the carcinogenicity and toxicity of metals.

4,272 citations


"Mitochondrial dysfunction and molec..." refers background in this paper

  • ...…reactive radicals include a wide-range of chemical species, including oxygen-, carbon-, and sulfurradicals originating from the superoxide radial, hydrogen peroxide, lipid peroxides, and also from chelates of amino acids, peptides, and proteins complexed with the toxic metals (Valko et al., 2005)....

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  • ...Arsenic inhibits pyruvate dehydrogenase (PDH) activity (Valko et al., 2005)....

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  • ...In addition, symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for collagen vascular disease, chronic fatigue syndrome, fibromyalgia, or psychosomatic illness” (Cohen and Gold, 2001)....

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  • ...Oxidative stress occurs in vitro and in vivo from both organic and inorganic mercury via their high affinity for binding thiols (sulfur-containing molecules), and the depletion of mitochondrial glutathione (Valko et al., 2005)....

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  • ...Toxic metals, especially mercury, generate many of their deleterious effects through the formation of free radicals, resulting in DNA damage, lipid peroxidation, depletion of protein sulfhydryls (eg, glutathione) and other effects (Valko et al., 2005)....

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Journal ArticleDOI
TL;DR: Substantial proportions of global disease burden are attributable to these major risks, to an extent greater than previously estimated.

3,654 citations


"Mitochondrial dysfunction and molec..." refers background in this paper

  • ...Medical research has found that iron-deficiency anemia is a major contributor to the global burden of disease, affecting an estimated 2 billion people, mostly women and children (DarntonHill et al., 2005; Ezzati et al., 2002)....

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