Tissue-specific differences in mitochondrial activity and biogenesis

Fernández-Vizarra, Erika; Enríquez, José Antonio; Pérez‐Martos, Acisclo; Montoya, Julio; Fernández‐Silva, Patricio

doi:10.1016/j.mito.2010.09.011

Cited by 152 publications

(122 citation statements)

References 48 publications

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“…Table 1 shows that CS activity/nDNA ratio varies greatly between tissues, again reflecting the tissue-specific differences in mitochondrial activities. As expected, the heart shows the highest ratio in all three individuals, in accordance with mtDNA relative abundance values and evidence that it has the highest mitochondrial content per cell (Fernandez-Vizarra et al, 2011). Moreover, the CS activity/mtDNA also differs markedly between samples, with higher values for heart, skeletal muscle and brain ( Table 1).…”

Section: Determination Of Mitochondrial Mass and Tissue Energy Requirsupporting

confidence: 84%

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

et al. 2015

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Eukaryotic cells contain a population of mitochondria, variable in number and shape, which in turn contain multiple copies of a tiny compact genome (mtDNA) whose expression and function is strictly coordinated with the nuclear one. mtDNA copy number varies between different cell or tissues types, both in response to overall metabolic and bioenergetics demands and as a consequence or cause of specific pathological conditions. Here we present a novel and reliable methodology to assess the effective mtDNA copy number per diploid genome by investigating off-target reads obtained by whole-exome sequencing (WES) experiments. We also investigate whether and how mtDNA copy number correlates with mitochondrial mass, respiratory activity and expression levels. Analyzing six different tissues from three age- and sex-matched human individuals, we found a highly significant linear correlation between mtDNA copy number estimated by qPCR and the frequency of mtDNA off target WES reads. Furthermore, mtDNA copy number showed highly significant correlation with mitochondrial gene expression levels as measured by RNA-Seq as well as with mitochondrial mass and respiratory activity. Our methodology makes thus feasible, at a large scale, the investigation of mtDNA copy number in diverse cell-types, tissues and pathological conditions or in response to specific treatments.

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Section: Determination Of Mitochondrial Mass and Tissue Energy Requirsupporting

confidence: 84%

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

et al. 2015

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“…We found that the tissues with the highest MtDNA content were heart and kidney, and surprisingly, the lowest MtDNA content was found in lung, being even lower than whole peripheral blood. These findings correlate with results reported by others in human (36) and in rat tissues (37). It would be interesting to determine if MtDNA content in different organs and cell types is indicative of bioenergetic function, and whether tissues such as heart and kidney, which contain the highest levels of MtDNA, are more prone to MtDNA damage and MtDNA mediated inflammation.…”

supporting

confidence: 88%

Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences

2016

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(2016). Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences. MITOCHONDRION. DOI: 10.1016DOI: 10. /j.mito.2016 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policyIf you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbbreviationsMtDNA-mitochondrial DNA NumtS-nuclear mitochondrial insertion sequence A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 Abstract:Background: Mitochondria contain extra-nuclear genome in the form of mitochondrial DNA (MtDNA), damage to which can lead to inflammation and bioenergetic deficit. Changes inMtDNA levels are increasingly used as a biomarker of mitochondrial dysfunction. We previously reported that in humans, fragments in the nuclear genome known as nuclear mitochondrial insertion sequences (NumtS) affect accurate quantification of MtDNA. In the current paper our aim was to determine whether mouse NumtS affect the quantification ofMtDNA and to establish a method designed to avoid this. Methods:The existence of NumtS in the mouse genome was confirmed using blast N, unique MtDNA regions were identified using FASTA, and MtDNA primers which do not co-amplify NUMTs were designed and tested. MtDNA copy numbers were determined in a range of mouse tissues as the ratio of the mitochondrial and nuclea...

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“…Correlation between the number of heteroplasmic sites and age for each tissue. The label for each plot indicates the tissue, correlation coefficient, and P value for the null hypothesis that the correlation coefficient is equal to 0. mitochondria in different tissues (22). Because all of the positions that exhibit this tissue/allele-related behavior are in the CR, it seems likely that regulation of mtDNA stability, replication, and/or transcription is involved, as suggested previously for CR heteroplasmies (11).…”

Section: Resultssupporting

confidence: 54%

Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations

Schröder

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Heteroplasmy in human mtDNA may play a role in cancer, other diseases, and aging, but patterns of heteroplasmy variation across different tissues have not been thoroughly investigated. Here, we analyzed complete mtDNA genome sequences at ∼3,500× average coverage from each of 12 tissues obtained at autopsy from each of 152 individuals. We identified 4,577 heteroplasmies (with an alternative allele frequency of at least 0.5%) at 393 positions across the mtDNA genome. Surprisingly, different nucleotide positions (nps) exhibit high frequencies of heteroplasmy in different tissues, and, moreover, heteroplasmy is strongly dependent on the specific consensus allele at an np. All of these tissue-related and allele-related heteroplasmies show a significant age-related accumulation, suggesting positive selection for specific alleles at specific positions in specific tissues. We also find a highly significant excess of liver-specific heteroplasmies involving nonsynonymous changes, most of which are predicted to have an impact on protein function. This apparent positive selection for reduced mitochondrial function in the liver may reflect selection to decrease damaging byproducts of liver mitochondrial metabolism (i.e., "survival of the slowest"). Overall, our results provide compelling evidence for positive selection acting on some somatic mtDNA mutations.mtDNA | heteroplasmy | selection | human | tissue variation

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Tissue-specific differences in mitochondrial activity and biogenesis

Cited by 152 publications

References 48 publications

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

Accurate quantification of mouse mitochondrial DNA without co-amplification of nuclear mitochondrial insertion sequences

Extensive tissue-related and allele-related mtDNA heteroplasmy suggests positive selection for somatic mutations

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