Mitochondrial haplogroup H and Alzheimer's disease—Is there a connection?

Maruszak, Aleksandra; Canter, Jeffrey A.; Styczyńska, Maria; Żekanowski, Cezary; Barcikowska, Maria

doi:10.1016/j.neurobiolaging.2008.01.004

Cited by 77 publications

(57 citation statements)

References 49 publications

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“…This transition is characteristic of particular mtDNA haplogroup H subgroups (164,227). To date, some studies have found haplogroup H is relatively over-represented in AD cohorts (86,173,174,227). As a potentially related finding, haplogroup H may represent a particularly well-coupled haplogroup, which infers that individuals with haplogroup H may produce more ROS than individuals with other haplogroups (171).…”

Section: Swerdlowmentioning

confidence: 99%

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Swerdlow

2012

Antioxidants & Redox Signaling

172

186

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Section: Swerdlowmentioning

confidence: 99%

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Swerdlow

2012

Antioxidants & Redox Signaling

172

186

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“…This modulation is carried out either directly by influencing energy production efficiency (Baudouin et al 2005), or indirectly by interaction with nuclear genes (Ryan and Hoogenraad 2007). In humans, the involvement of nuclear-mitochondrial interactions in modulating complex phenotypes is supported by the observation of non-random associations between mtDNA and nuclear variability (De Benedictis et al 2000;Carrieri et al 2001;Maruszak et al 2008). In mice, by means of conplastic strains expressing different combinations of mitochondrial/nuclear genomes, it has been unequivocally demonstrated that mtDNA variability affects complex phenotypes, such as hearing loss (Johnson et al 2001), cognitive function (Robertoux et al 2003) and risk of type 2 diabetes (Pravenec et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Bellizzi

Taverna

D’Aquila

et al. 2009

Cell Stress and Chaperones

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To explore possible relationships between mitochondrial DNA (mtDNA) polymorphism and the expression levels of stress-responder nuclear genes we assembled five cybrid cell lines by repopulating 143B.TK − cells, depleted of their own mtDNA (Rho 0 cells), with foreign mitochondria with different mtDNA sequences (lines H, J, T, U, X). We evaluated, at both basal and under heat stress conditions, gene expression (mRNA) and intra-mitochondrial protein levels of HSP60 and HSP75, two key components in cellular stress response. At basal conditions, the levels of HSP60 and HSP75 mRNA were lower in one cybrid (H) than in the others (p=0.005 and p=0.001, respectively). Under stress conditions, the H line over-expressed both genes, so that the inter-cybrid difference was abolished. Moreover, the HSP60 intra-mitochondrial protein levels differed among the cybrid lines (p=0.001), with levels higher in H than in the other cybrid lines. On the whole, our results provide further experimental evidence that mtDNA variability influences the cell response to stressful conditions by modulating components involved in this response. Sentence summary of the article: the results reported in the present study provide important experimental evidence that in human cells mtDNA variability is able to influence the cellular response to heat stress by modulating both the transcription of genes involved in this response and their intra-mitochondrial protein levels.

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“…28,29 This means that each haplogroup, with its different set of SNPs, can have unique bioenergetic properties and responses to oxidative stressors. The risks of developing PD and AD within the Western European are higher among mtDNA haplogroup H, but lower for haplogroups J and K. 30,31 It is possible that the haplogroup H has significantly higher mitochondrial oxidative damage and higher VO (2max) (oxygen consumption) to produce more ROS. 32 It seems to be that the association between haplogroup U and the risks of sCJD needs further assays in a larger sample scale.…”

Section: Discussionmentioning

confidence: 99%

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt–Jakob disease

Zhang

et al. 2014

Eur J Hum Genet

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Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause a variety of chronic diseases in central nervous system (CNS). However, the role of mtDNA mutations in sporadic Creutzfeldt-Jakob disease (sCJD) has still been unknown. In this study, we comparatively analyzed complete mtDNA sequences of 31 Chinese sCJD patients and 32 controls. Using MITOMASTER and PhyloTree, we characterized 520 variants in sCJD patients and 507 variants in control by haplogroup and allele frequencies. We classified the mtDNAs into 40 sub-haplogroups of 5 haplogroups, most of them being Asian-specific haplogroups. Haplogroup U, an European-specific haplogroups mtDNA, was found only in sCJD. The analysis to control region (CR) revealed a 31% increase in the frequency of mtDNA CR mutations in sCJD versus controls. In functional elements of the mtDNA CR, six CR mutations were in conserved sequence blocks I (CSBI) in sCJD, while only one in control (Po0.05). More mutants in transfer ribonucleic acid-Leu (tRNA-Leu) were detected in sCJD. The frequencies of two synonymous amino-acid changes, m.11467A4G, p.( ¼ ) in NADH dehydrogenase subunit 4 (ND4) and m.12372G4A, p.( ¼ ) in NADH dehydrogenase subunit 5 (ND5), in sCJD patients were higher than that of controls. Our study, for the first time, screened the variations of mtDNA of Chinese sCJD patients and identified some potential disease-related mutations for further investigations.

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Mitochondrial haplogroup H and Alzheimer's disease—Is there a connection?

Cited by 77 publications

References 49 publications

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Mitochondria and Cell Bioenergetics: Increasingly Recognized Components and a Possible Etiologic Cause of Alzheimer's Disease

Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines

Analyses of the mitochondrial mutations in the Chinese patients with sporadic Creutzfeldt–Jakob disease

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