Elsevier

Mitochondrion

Volume 53, July 2020, Pages 214-223
Mitochondrion

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

https://doi.org/10.1016/j.mito.2020.06.004Get rights and content
Under a Creative Commons license
open access

Highlights

  • mtDNA-CN, a proxy for mitochondrial function, is associated with chronic disease.

  • mtDNA-CN can be measured from pre-existing microarray and sequencing data.

  • Mitochondrial dysfunction leads to gene expression changes of relevant pathways.

  • mtDNA-CN shows promise as a potential biomarker for chronic disease.

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

mitochondrial DNA
Clinical biomarker
mtDNA
Complex disease

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