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Chieppa M, Kashyrina M, Miraglia A, Vardanyan D. Enhanced CRC Growth in Iron-Rich Environment, Facts and Speculations. Int J Mol Sci 2024; 25:12389. [PMID: 39596454 PMCID: PMC11594836 DOI: 10.3390/ijms252212389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/07/2024] [Accepted: 11/11/2024] [Indexed: 11/28/2024] Open
Abstract
The contribution of nutritional factors to disease development has been demonstrated for several chronic conditions including obesity, type 2 diabetes, metabolic syndrome, and about 30 percent of cancers. Nutrients include macronutrients and micronutrients, which are required in large and trace quantities, respectively. Macronutrients, which include protein, carbohydrates, and lipids, are mainly involved in energy production and biomolecule synthesis; micronutrients include vitamins and minerals, which are mainly involved in immune functions, enzymatic reactions, blood clotting, and gene transcription. Among the numerous micronutrients potentially involved in disease development, the present review will focus on iron and its relation to tumor development. Recent advances in the understanding of iron-related proteins accumulating in the tumor microenvironment shed light on the pivotal role of iron availability in sustaining pathological tumor hallmarks, including cell cycle regulation, angiogenesis, and metastasis.
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Affiliation(s)
- Marcello Chieppa
- Department of Experimental Medicine, University of Salento Centro Ecotekne, S.P.6, 73100 Lecce, Italy; (M.K.); (D.V.)
| | - Marianna Kashyrina
- Department of Experimental Medicine, University of Salento Centro Ecotekne, S.P.6, 73100 Lecce, Italy; (M.K.); (D.V.)
| | - Alessandro Miraglia
- Institute of Science of Food Production, Unit of Lecce, C.N.R., 73100 Lecce, Italy;
| | - Diana Vardanyan
- Department of Experimental Medicine, University of Salento Centro Ecotekne, S.P.6, 73100 Lecce, Italy; (M.K.); (D.V.)
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Nevoit G, Jarusevicius G, Potyazhenko M, Mintser O, Bumblyte IA, Vainoras A. Mitochondrial Dysfunction and Risk Factors for Noncommunicable Diseases: From Basic Concepts to Future Prospective. Diseases 2024; 12:277. [PMID: 39589951 PMCID: PMC11592525 DOI: 10.3390/diseases12110277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 10/24/2024] [Accepted: 10/24/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND/OBJECTIVES Noncommunicable diseases (NCDs) are a very important medical problem. The key role of mitochondrial dysfunction (MD) in the occurrence and progression of NCDs has been proven. However, the etiology and pathogenesis of MD itself in many NCDs has not yet been clarified, which makes it one of the most serious medical problems in the modern world, according to many scientists. METHODS An extensive research in the literature was implemented in order to elucidate the role of MD and NCDs' risk factors in the pathogenesis of NCDs. RESULTS The authors propose to take a broader look at the problem of the pathogenesis of NCDs. It is important to understand exactly how NCD risk factors lead to MD. The review is structured in such a way as to answer this question. Based on a systematic analysis of scientific data, a theoretical concept of modern views on the occurrence of MD under the influence of risk factors for the occurrence of NCDs is presented. This was done in order to update MD issues in clinical medicine. MD and NCDs progress throughout a patient's life. Based on this, the review raised the question of the existence of an NCDs continuum. CONCLUSIONS MD is a universal mechanism that causes organ dysfunction and comorbidity of NCDs. Prevention of MD involves diagnosing and eliminating the factors that cause it. Mitochondria are an important therapeutic target.
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Affiliation(s)
- Ganna Nevoit
- Laboratory of Population Studies, Cardiology Institute, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania
| | - Gediminas Jarusevicius
- Laboratory for Automatization of Cardiovascular Investigations, Cardiology Institute, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania;
| | - Maksim Potyazhenko
- Department of Internal Medicine and Emergency Medicine, Poltava State Medical University, 36011 Poltava, Ukraine;
| | - Ozar Mintser
- Department of Fundamental Disciplines and Informatics, Shupyk National Healthcare University of Ukraine, 04112 Kyiv, Ukraine;
| | - Inga Arune Bumblyte
- Department of Nephrology, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania;
| | - Alfonsas Vainoras
- Laboratory for Automatization of Cardiovascular Investigations, Cardiology Institute, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania;
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Wu Z, Fang ZX, Hou YY, Wu BX, Deng Y, Wu HT, Liu J. Review of ferroptosis in colorectal cancer: Friends or foes? World J Gastroenterol 2023; 29:469-486. [PMID: 36688016 PMCID: PMC9850932 DOI: 10.3748/wjg.v29.i3.469] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/30/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Ferroptosis is a newly discovered type of cell-regulated death. It is characterized by the accumulation of iron-dependent lipid peroxidation and can be distinguished from other forms of cell-regulated death by different morphology, biochemistry, and genetics. Recently, studies have shown that ferroptosis is associated with a variety of diseases, including liver, kidney and neurological diseases, as well as cancer. Ferroptosis has been shown to be associated with colorectal epithelial disorders, which can lead to cancerous changes in the gut. However, the potential role of ferroptosis in the occurrence and development of colorectal cancer (CRC) is still controversial. To elucidate the underlying mechanisms of ferroptosis in CRC, this article systematically reviews ferroptosis, and its cellular functions in CRC, for furthering the understanding of the pathogenesis of CRC to aid clinical treatment.
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Affiliation(s)
- Zheng Wu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Ze-Xuan Fang
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yan-Yu Hou
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Bing-Xuan Wu
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Yu Deng
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Hua-Tao Wu
- Department of General Surgery, First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
| | - Jing Liu
- Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Breast Cancer, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong Province, China
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Bomer N, Pavez-Giani MG, Grote Beverborg N, Cleland JGF, van Veldhuisen DJ, van der Meer P. Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism? J Intern Med 2022; 291:713-731. [PMID: 35137472 PMCID: PMC9303299 DOI: 10.1111/joim.13456] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Heart failure is a devastating clinical syndrome, but current therapies are unable to abolish the disease burden. New strategies to treat or prevent heart failure are urgently needed. Over the past decades, a clear relationship has been established between poor cardiac performance and metabolic perturbations, including deficits in substrate uptake and utilization, reduction in mitochondrial oxidative phosphorylation and excessive reactive oxygen species production. Together, these perturbations result in progressive depletion of cardiac adenosine triphosphate (ATP) and cardiac energy deprivation. Increasing the delivery of energy substrates (e.g., fatty acids, glucose, ketones) to the mitochondria will be worthless if the mitochondria are unable to turn these energy substrates into fuel. Micronutrients (including coenzyme Q10, zinc, copper, selenium and iron) are required to efficiently convert macronutrients to ATP. However, up to 50% of patients with heart failure are deficient in one or more micronutrients in cross-sectional studies. Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation, moving our view of the failing myocardium away from an "an engine out of fuel" to "a defective engine on a path to self-destruction." This summary of evidence suggests that supplementation with micronutrients-preferably as a package rather than singly-might be a potential therapeutic strategy in the treatment of heart failure patients.
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Affiliation(s)
- Nils Bomer
- Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Mario G Pavez-Giani
- Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Niels Grote Beverborg
- Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
| | - John G F Cleland
- Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK.,National Heart & Lung Institute, Royal Brompton and Harefield Hospitals, Imperial College, London, UK
| | - Dirk J van Veldhuisen
- Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
| | - Peter van der Meer
- Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands
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Jiao L, Dai T, Lu J, Tao X, Jin M, Sun P, Zhou Q. Excess iron supplementation induced hepatopancreas lipolysis, destroyed intestinal function in Pacific white shrimp Litopenaeus vannamei. MARINE POLLUTION BULLETIN 2022; 176:113421. [PMID: 35183027 DOI: 10.1016/j.marpolbul.2022.113421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 12/08/2021] [Accepted: 01/30/2022] [Indexed: 06/14/2023]
Abstract
So far, the adverse effects of excess Fe in shrimp have been ignored for years as it was thought that extra Fe supplementation was not needed in the practical diets. Nowadays, Fe concentration in commercial shrimp feed from feed enterprises could be around 301.34-545.5 mg/kg, which is mainly due to the fish meal containing up to 1500 mg/kg Fe. Therefore, the purpose of this experiment was to investigate the effects of Fe supplementation on the growth performance, tissue Fe deposition, hepatopancreas lipid metabolism, intestinal function in L. vannamei. The results showed that although growth performance was not influenced by the dietary Fe supplementation, excess Fe supplementation (955.00 mg/kg) significantly increased hepatopancreas Fe deposition and induced lipolysis. Moreover, excess Fe supplementation impaired intestinal immune function and disrupted microbiota homeostasis. These findings might provide partial theoretical evidence for the effect of dietary Fe supplementation on physiological metabolism in L. vannamei.
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Affiliation(s)
- Lefei Jiao
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Tianmeng Dai
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Jingjing Lu
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Xinyue Tao
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Min Jin
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Peng Sun
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China
| | - Qicun Zhou
- Laboratory of Fish Nutrition, School of Marine Sciences, Ningbo University, Ningbo 315211, PR China.
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The Multifaceted Regulation of Mitochondria in Ferroptosis. Life (Basel) 2021; 11:life11030222. [PMID: 33801920 PMCID: PMC8001967 DOI: 10.3390/life11030222] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 02/27/2021] [Accepted: 03/05/2021] [Indexed: 01/03/2023] Open
Abstract
Ferroptosis is characterized as a novel form of regulated cell death, which is initiated by the lethal accumulation of lipid peroxidation catalyzed by cellular labile free iron. This iron driven cell death sharply differs from other well characterized forms of regulated cell death at morphological, genetic and biochemical levels. Increasing research has elaborated a high relevance between dysregulated ferroptosis and the pathogenesis of degenerative diseases and organs injury in human patients. Additionally, targeted induction of ferroptosis is considered as a potentially therapeutic design for the clinical intervention of other therapy-resistant cancers. It is well understood that mitochondria, the cellular powerhouse, determine several types of regulated cell death. Recently, compromised mitochondrial morphology and functionalities have been primarily formulated in ferroptosis. Several mitochondria associated proteins and metabolic processes have been elaborated to fine-tune ferroptotic program. Herein, we critically review the recent advances in this booming field, with focus on summarizing the multifaceted mitochondrial regulation of ferroptosis and providing a perspective on the potential biochemical basis. Finally, we are attempting to shed light on an integrative view on the possibility of mitochondria- and ferroptosis-targeting therapeutics as novel treatment designs for the intervention of ferroptosis related diseases.
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Rines AK, Ardehali H. Transition metals and mitochondrial metabolism in the heart. J Mol Cell Cardiol 2012; 55:50-7. [PMID: 22668786 DOI: 10.1016/j.yjmcc.2012.05.014] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2012] [Revised: 05/23/2012] [Accepted: 05/25/2012] [Indexed: 12/12/2022]
Abstract
Transition metals are essential to many biological processes in almost all organisms from bacteria to humans. Their versatility, which arises from an ability to undergo reduction-oxidation chemistry, enables them to act as critical cofactors of enzymes throughout the cell. Accumulation of metals, however, can also lead to oxidative stress and cellular damage. The importance of metals to both enzymatic reactions and oxidative stress makes them key players in mitochondria. Mitochondria are the primary energy-generating organelles of the cell that produce ATP through a chain of enzymatic complexes that require transition metals, and are highly sensitive to oxidative damage. Moreover, the heart is one of the most mitochondrially-rich tissues in the body, making metals of particular importance to cardiac function. In this review, we focus on the current knowledge about the role of transition metals (specifically iron, copper, and manganese) in mitochondrial metabolism in the heart. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
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Affiliation(s)
- Amy K Rines
- Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
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Zhou X, Li N, Wang Y, Wang Y, Zhang X, Zhang H. Effects of X-irradiation on mitochondrial DNA damage and its supercoiling formation change. Mitochondrion 2011; 11:886-92. [DOI: 10.1016/j.mito.2011.07.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2010] [Revised: 05/04/2011] [Accepted: 07/22/2011] [Indexed: 01/18/2023]
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10
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Fernández-Vizarra E, Enriquez JA, Pérez-Martos A, Montoya J, Fernández-Silva P. Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones. Curr Genet 2008; 54:13-22. [PMID: 18481068 DOI: 10.1007/s00294-008-0194-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2008] [Revised: 04/24/2008] [Accepted: 04/27/2008] [Indexed: 01/17/2023]
Abstract
Biogenesis of the oxidative phosphorylation system (OXPHOS) requires the coordinated expression of the nuclear and the mitochondrial genomes. Thyroid hormones play an important role in cell growth and differentiation and are one of the main effectors in mitochondrial biogenesis. To determine how mtDNA expression is regulated, we have investigated the response of two different tissues, the heart and liver, to the thyroid hormone status in vivo and in vitro. We show here that mtDNA expression is a tightly regulated process and that several levels of control can take place simultaneously. In addition, we show that the mechanisms operating in the control of mtDNA expression and their relevance differ between the two tissues, being gene dosage important only in heart while transcription rate and translation efficiency have more weight in liver cells. Another interesting difference is the lack of a direct effect of thyroid hormones on heart mitochondrial transcription.
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Affiliation(s)
- Erika Fernández-Vizarra
- Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, Zaragoza, Spain
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Chen J, Kadlubar FF, Chen JZ. DNA supercoiling suppresses real-time PCR: a new approach to the quantification of mitochondrial DNA damage and repair. Nucleic Acids Res 2007; 35:1377-88. [PMID: 17284464 PMCID: PMC1851651 DOI: 10.1093/nar/gkm010] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
As a gold standard for quantification of starting amounts of nucleic acids, real-time PCR is increasingly used in quantitative analysis of mtDNA copy number in medical research. Using supercoiled plasmid DNA and mtDNA modified both in vitro and in cancer cells, we demonstrated that conformational changes in supercoiled DNA have profound influence on real-time PCR quantification. We showed that real-time PCR signal is a positive function of the relaxed forms (open circular and/or linear) rather than the supercoiled form of DNA, and that the conformation transitions mediated by DNA strand breaks are the main basis for sensitive detection of the relaxed DNA. This new finding was then used for sensitive detection of structure-mediated mtDNA damage and repair in stressed cancer cells, and for accurate quantification of total mtDNA copy number when all supercoiled DNA is converted into the relaxed forms using a prior heat-denaturation step. The new approach revealed a dynamic mtDNA response to oxidative stress in prostate cancer cells, which involves not only early structural damage and repair but also sustained copy number reduction induced by hydrogen peroxide. Finally, the supercoiling effect should raise caution in any DNA quantification using real-time PCR.
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Affiliation(s)
- Jinsong Chen
- Department of Surgery, Division of Urology, McGill University Health Centre and Research Institute, Montreal, Quebec H3G 1A4, Canada and Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Fred F. Kadlubar
- Department of Surgery, Division of Urology, McGill University Health Centre and Research Institute, Montreal, Quebec H3G 1A4, Canada and Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - Junjian Z. Chen
- Department of Surgery, Division of Urology, McGill University Health Centre and Research Institute, Montreal, Quebec H3G 1A4, Canada and Department of Epidemiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
- *To whom correspondence should be addressed. Tel: +1 514 934 1934 x 44601(o); Fax: +1 514 934 8261;
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Templeton DM, Liu Y. Genetic regulation of cell function in response to iron overload or chelation. BIOCHIMICA ET BIOPHYSICA ACTA 2003; 1619:113-24. [PMID: 12527106 DOI: 10.1016/s0304-4165(02)00497-x] [Citation(s) in RCA: 82] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Iron influences many aspects of cell function on different biochemical levels. This review considers effects mediated through iron-dependent changes in gene expression in mammalian cells. Several classes of related genes are responsive to cellular iron levels, but no clear patterns readily account for the toxicity of iron overload or the consequences of removal of iron with chelating agents. Here we group some of the genes influenced by iron status into those related to iron metabolism, oxygen and oxidative stress, energy metabolism, cell cycle regulation, and tissue fibrosis. Iron excess and chelation do not generally result in a continuous or graded transcriptional response, but indicate operation of distinct mechanisms. An emerging concept is that iron signals through generation of reactive oxygen species to activate transcription factors such as NF-kappaB, whereas iron removal mimics hypoxia, perhaps by disrupting iron-based O(2) sensors and influencing gene expression through, e.g., the hypoxia-inducible factor, HIF-1. Heme and other metalloporphyrins have other distinct mechanisms for regulating transcription. Regulation of gene expression through iron-responsive elements in mRNAs coded by several genes is one of the best understood mechanisms of translational control.
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Affiliation(s)
- Douglas M Templeton
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
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Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, Viteri FE, Ames BN. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci U S A 2002; 99:2264-9. [PMID: 11854522 PMCID: PMC122353 DOI: 10.1073/pnas.261708798] [Citation(s) in RCA: 255] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Approximately two billion people, mainly women and children, are iron deficient. Two studies examined the effects of iron deficiency and supplementation on rats. In study 1, mitochondrial functional parameters and mitochondrial DNA (mtDNA) damage were assayed in iron-deficient (< or =5 microg/day) and iron-normal (800 microg/day) rats and in both groups after daily high-iron supplementation (8,000 microg/day) for 34 days. This dose is equivalent to the daily dose commonly given to iron-deficient humans. Iron-deficient rats had lower liver mitochondrial respiratory control ratios and increased levels of oxidants in polymorphonuclear-leukocytes, as assayed by dichlorofluorescein (P < 0.05). Rhodamine 123 fluorescence of polymorphonuclear-leukocytes also increased (P < 0.05). Lowered respiratory control ratios were found in daily high-iron-supplemented rats regardless of the previous iron status (P < 0.05). mtDNA damage was observed in both iron-deficient rats and rats receiving daily high-iron supplementation, compared with iron-normal rats (P < 0.05). Study 2 compared iron-deficient rats given high doses of iron (8,000 microg) either daily or every third day and found that rats given iron supplements every third day had less mtDNA damage on the second and third day after the last dose compared to daily high iron doses. Both inadequate and excessive iron (10 x nutritional need) cause significant mitochondrial malfunction. Although excess iron has been known to cause oxidative damage, the observation of oxidant-induced damage to mitochondria from iron deficiency has been unrecognized previously. Untreated iron deficiency, as well as excessive-iron supplementation, are deleterious and emphasize the importance of maintaining optimal iron intake.
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Affiliation(s)
- Patrick B Walter
- Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
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