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

Authors

Christina A. Castellani, Johns Hopkins School of MedicineFollow
Ryan J. Longchamps, Johns Hopkins School of Medicine
Jing Sun, Johns Hopkins Bloomberg School of Public Health
Eliseo Guallar, Johns Hopkins Bloomberg School of Public Health
Dan E. Arking, Johns Hopkins School of Medicine

Document Type

Article

Publication Date

7-1-2020

Journal

Mitochondrion

Volume

53

First Page

214

Last Page

223

URL with Digital Object Identifier

10.1016/j.mito.2020.06.004

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.