Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jul:53:214-223.
doi: 10.1016/j.mito.2020.06.004. Epub 2020 Jun 13.

Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease

Christina A Castellani  1 , Ryan J Longchamps  1 , Jing Sun  2 , Eliseo Guallar  3 , Dan E Arking  4
Affiliations
Review

Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease

Christina A Castellani et al. Mitochondrion. 2020 Jul.

Abstract

Mitochondrial DNA copy number (mtDNA-CN) is a biomarker of mitochondrial function and levels of mtDNA-CN have been reproducibly associated with overall mortality and a number of age-related diseases, including cardiovascular disease, chronic kidney disease, and cancer. Recent advancements in techniques for estimating mtDNA-CN, in particular the use of DNA microarrays and next-generation sequencing data, have led to the comprehensive assessment of mtDNA-CN across these and other diseases and traits. The importance of mtDNA-CN measures to disease and these advancing technologies suggest the potential for mtDNA-CN to be a useful biomarker in the clinic. While the exact mechanism(s) underlying the association of mtDNA-CN with disease remain to be elucidated, we review the existing literature which supports roles for inflammatory dynamics, immune function and alterations to cell signaling as consequences of variation in mtDNA-CN. We propose that future studies should focus on characterizing longitudinal, cell-type and cross-tissue profiles of mtDNA-CN as well as improving methods for measuring mtDNA-CN which will expand the potential for its use as a clinical biomarker.

Keywords: Clinical biomarker; Complex disease; mitochondrial DNA; mtDNA.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Summary of proposed relationship between mtDNA-CN and disease.
See this image and copyright information in PMC

References

    1. Aggarwal NT, Makielski JC, 2013. Redox control of cardiac excitability. Antioxid. Redox Signal 18, 432–468. 10.1089/ars.2011.4234 - DOI - PMC - PubMed
    1. Amor S, Puentes F, Baker D, van der Valk P, 2010. Inflammation in neurodegenerative diseases. Immunology 129, 154–169. 10.1111/j.1365-2567.2009.03225.x - DOI - PMC - PubMed
    1. Ashar FN, Moes A, Moore AZ, Grove ML, Chaves PHM, Coresh J, Newman AB, Matteini AM, Bandeen-Roche K, Boerwinkle E, Walston JD, Arking DE, 2015. Association of mitochondrial DNA levels with frailty and all-cause mortality. J. Mol. Med. Berl. Ger 93, 177–186. 10.1007/s00109-014-1233-3 - DOI - PMC - PubMed
    1. Ashar FN, Zhang Y, Longchamps RJ, Lane J, Moes A, Grove ML, Mychaleckyj JC, Taylor KD, Coresh J, Rotter JI, Boerwinkle E, Pankratz N, Guallar E, Arking DE, 2017. Association of Mitochondrial DNA Copy Number With Cardiovascular Disease. JAMA Cardiol. 2, 1247–1255. 10.1001/jamacardio.2017.3683 - DOI - PMC - PubMed
    1. Bai R-K, Wong L-JC, 2005. Simultaneous Detection and Quantification of Mitochondrial DNA Deletion(s), Depletion, and Over-Replication in Patients with Mitochondrial Disease. J. Mol. Diagn 7, 613–622. 10.1016/S1525-1578(10)60595-8 - DOI - PMC - PubMed

Publication types

Substances

LinkOut - more resources