Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity
Open accessAbstract
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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On average, a human cell could contain from a minimum of 0.09 ± 0.0067 cm to a maximum of 3.62 ± 0.15 cm of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell.
“On average, a human cell could contain from a minimum of 2,845,394 ± 204,296 bp, 0.09 ± 0.0067 cm and 0.0029 ± 0.00021 pg to a maximum of 110,742,060 ± 4,568,736.06 bp, 3.62 ± 0.15 cm and 0.11 ± 0.0047 pg of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell [40] (Additional file 1: Additional Methods).”
From On the length, weight and GC content of the human genome (2019) · cites this paper as [40]
The Introduction states that a mitochondrial genome is around 16.5 kbp long, and the section ‘mtDNA copy number per diploid nuclear genome determined by qPCR’ reports that copy number varies among human tissues. Our copy does not give the claimed 0.09 ± 0.0067 to 3.62 ± 0.15 cm range or its uncertainty; those quantitative lengths are not supported by the cited text. (LLM, conf=0.78)
Experimental — accuracy not yet measuredOn average, a human cell could contain from a minimum of 0.0029 ± 0.00021 pg to a maximum of 0.11 ± 0.0047 pg of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell.
“On average, a human cell could contain from a minimum of 2,845,394 ± 204,296 bp, 0.09 ± 0.0067 cm and 0.0029 ± 0.00021 pg to a maximum of 110,742,060 ± 4,568,736.06 bp, 3.62 ± 0.15 cm and 0.11 ± 0.0047 pg of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell [40] (Additional file 1: Additional Methods).”
From On the length, weight and GC content of the human genome (2019) · cites this paper as [40]
The Introduction (page unavailable) says that the mitochondrial genome is about 16.5 kbp long and that mtDNA copy number varies, providing a basis for estimating DNA per cell. It does not report the claimed 0.0029 ± 0.00021 to 0.11 ± 0.0047 pg range or its uncertainties; searches for those values found no matching passage. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOn average, a human cell could contain from a minimum of 2,845,394 ± 204,296 bp to a maximum of 110,742,060 ± 4,568,736.06 bp of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell.
“On average, a human cell could contain from a minimum of 2,845,394 ± 204,296 bp, 0.09 ± 0.0067 cm and 0.0029 ± 0.00021 pg to a maximum of 110,742,060 ± 4,568,736.06 bp, 3.62 ± 0.15 cm and 0.11 ± 0.0047 pg of mtDNA in total, depending on the uncertainty of the number DNA molecules per cell [40] (Additional file 1: Additional Methods).”
From On the length, weight and GC content of the human genome (2019) · cites this paper as [40]
The Introduction (page unavailable) describes an mtDNA genome of around 16.5 kbp and says copy number varies per cell. The qPCR Results section (page unavailable) also reports variation across six tissues, but our copy does not give the claimed minimum and maximum base-pair totals or their uncertainties; searches for those figures and corresponding copy numbers found no match. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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References 55 · Cited by 197
Research works printed but not linked: 2
- S. Di Mauro, E. BonillaA. Engel, C.F.-A. (Eds.), Myology, vol. II, Mc Grav Hill, Philadelphia (2004), pp. 1623-1676
- A. Draxl, A. Eigentler, E. Gnaiger PBI-Shredder HRR-Set: preparation of tissue homogenates for diagnosis of mitochondrial respiratory function Mitochondrial Physiol. Netw., 17 (02) (2013), pp. 1-8
- Authors
- D'Erchia, A. M., Atlante, A., Gadaleta, G., Pavesi, G., Chiara, M., De Virgilio, C., Manzari, C., Mastropasqua, F., Prazzoli, G. M., Picardi, E., Gissi, C., Horner, D., Reyes, A., Sbisà, E., Tullo, A., & Pesole, G.
- Affiliations
- Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IT)
- University of Bari Aldo Moro (IT)
- University of Milan (IT)
- MRC Mitochondrial Biology Unit (GB)
- Institute of Biomedical Technologies (IT)
- Corresponding author
- Pesole, Graziano
- ORCID
- Venue
- Mitochondrion
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 20
- Pages
- 13-21
- ISSN
- 1567-7249 (ISSN-L)
- OpenAlex
- W2059891246
- Cited by
- 197
- References
- 55
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 16 · 2023: 32 · 2022: 24 · 2021: 36 · 2020: 16 · 2019: 13 · 2018: 9 · 2017: 11 · 2016: 9 · 2015: 5
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Mitochondrion (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nd)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- mitochondrial DNA copy number, exome sequencing, mitochondrial transcription, mitochondrial mass, mitochondrial respiration, mitochondrial gene expression, human tissue
- MeSH terms
- DNA, Mitochondrial, Humans, Male, Middle Aged, Mitochondria, Transcription, Genetic, Gene Dosage, Cell Respiration, Exome
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