Mitochondria are the critical organelles involved in various cellular functions. Mitochondrial biogenesis is activated by multiple cellular mechanisms which require a synchronous regulation between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). The mitochondrial DNA copy number (mtDNA‑CN) is a proxy indicator for mitochondrial activity, and its alteration reflects mitochondrial biogenesis and function. Despite the precise mechanisms that modulate the amount and composition of mtDNA, which have not been fully elucidated, mtDNA‑CN is known to influence numerous cellular pathways that are associated with cancer and as well as multiple other diseases. In addition, the utility of current technology in measuring mtDNA‑CN contributes to its extensive assessment of diverse traits and tumorigenesis. The present review provides an overview of mtDNA‑CN variations across human cancers and an extensive summary of the existing knowledge on the regulation and machinery of mtDNA‑CN. The current information on the advanced methods used for mtDNA‑CN assessment is also presented.
Keywords: biomarker; cancer; mitochondrial DNA; mtDNA copy number alterations; mtDNA replication.