Mammalian mitochondrial nucleoids: Organizing an independently minded genome

Holt, Ian; He, Jin; Mao, Chih-Chieh; Boyd-Kirkup, Jerome D.; Martinsson, Peter; Sembongi, Hiroshi; Reyes, Aurelio; Spelbrink, Johannes N.

doi:10.1016/j.mito.2007.06.004

Cited by 139 publications

(109 citation statements)

References 43 publications

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“…There are just a few reports published about the size of mitochondrial nucleoids in mammals and a size of 0.1 to 0.3 μm was reported in cells transfected with Twinkle-GFP or cells imaged with antibodies against TFAM or mtSSB (18). A nucleoid size of 0.4 to 0.9 μm was reported with PicoGreen and antibodies against DNA in mammalian cells imaged by confocal microscopy (28). We did an extensive confocal microscopy image analysis of a panel of mammalian cell lines and found a mean nucleoid size of ∼270 nm, which is close to the lateral optical resolution limit of light microscopy.…”

Section: Discussionsupporting

confidence: 65%

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

Kukat

Wurm

Spåhr

et al. 2011

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

458

421

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Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of approximately 100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average approximately 1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging

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Section: Discussionsupporting

confidence: 65%

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

Kukat

Wurm

Spåhr

et al. 2011

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

458

421

View full text Add to dashboard Cite

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“…MtDNA is a double stranded DNA ring, packed into a nucleo-protein complex, called the nucleoid (Chen and Butow, 2005;Holt et al, 2007), lacks any introns and encodes for 13 proteins necessary for the assembly of the respiratory chain, 22 tRNAs and two ribosomal RNAs (Graeber et al, 1998). The general thinking for the past three decades has been that the ageing phenotype is a consequence of oxidative damage of proteins, lipids and DNA inflicted by free radicals which in turn are generated as normal byproducts of the oxidative phosphorylation (OXPHOS) (Miquel et al, 1980;Harman, 1981;Ames, 1989).…”

Section: Introductionmentioning

confidence: 99%

The 4977bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more?

Meißner

Bruse

Mohamed

et al. 2008

Experimental Gerontology

140

117

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It has been suggested that deletions of mitochondrial DNA (mtDNA) are important players with regard to the ageing process. Since the early 1990s, the 4977 bp deletion has been studied in various tissues, especially in postmitotic tissues with high energy demand. Unfortunately, some of these studies included less than 10 subjects, so the aim of our study was to quantify reliable the deletion amount in nine different regions of human brain, heart and skeletal muscle in a cohort of 92 individuals. The basal ganglia contain the highest deletion amounts with values up to 2.93% and differences in deletion levels between early adolescence and older ages were up to three orders of magnitude. Values in frontal lobe were on average an order of magnitude lower, but lowest in cerebellar tissue where the amount was on average only 5 x 10 -3 of the basal ganglia. The deletion started to accumulate in iliopsoas muscle early in the fourth decade of life with values between 0.00019% and 0.0035% and was highest in a 102 year-old woman with 0.14%. In comparison to skeletal muscle, the overall abundance in heart muscle of the left ventricle was only one third. The best linear logarithmic correlation between amount of the deletion and age was found in substanta nigra with r=0.87 (p<0.0005) followed by anterior wall of the left ventricle (r=0.82; p<0.0005). With regard to mitochondrial DNA damage, we propose to use the 4977 bp deletion as an ideal biomarker to discriminate between physiological ageing and accelerated ageing. The biological meaning of mitochondrial deletions in the process of ageing is under discussion, but there is experimental evidence that large-scale deletions impair the oxidative phosphorylation in single cells and sensitize these cells to undergo apoptosis.

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“…It is organized in vivo as protein-DNA complexes, known as mitochondrial nucleoids, with each nucleoid containing ϳ2-10 copies of the genome (1)(2)(3)(4). mtDNA is subject to constant attack by reactive oxygen species that are produced through metabolism in mitochondria.…”

mentioning

confidence: 99%

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

Mbantenkhu

Wang

Nardozzi

et al. 2011

Journal of Biological Chemistry

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Background:The mechanisms of homologous recombination and recombinational repair of double-stranded DNA breaks in mitochondria are poorly understood. Results: The yeast mitochondrial nucleoid protein, Mgm101, shares biochemical, structural, and functional similarities with the Rad52 family proteins. Conclusion: Mgm101 is a Rad52-related molecular component involved in mtDNA recombination Significance: This finding helps in understanding the mechanism of homologous recombination in mitochondria.

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Mammalian mitochondrial nucleoids: Organizing an independently minded genome

Cited by 139 publications

References 43 publications

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA

The 4977bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: A useful biomarker or more?

Mgm101 Is a Rad52-related Protein Required for Mitochondrial DNA Recombination

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