Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance

Table 3 Clinical relevance of mitochondrial DNA copy number in diseases

Disease category	Role of mtDNAcn	Key observations	Diagnostic/prognostic value
Neurodegenerative disorders[64-70]	Biomarker for disease progression and severity	Reduced mtDNAcn in AD brains; increased mtDNAcn in peripheral blood of AD patients	Correlates with tau pathology in CSF; potential for non-invasive diagnosis using blood mtDNA levels
Cancer[15,62,100-102]	Indicator of tumor aggressiveness and treatment response	Elevated mtDNAcn associated with tumor proliferation; decreased mtDNAcn linked to poor prognosis	Distinguishes between cancerous and non-cancerous tissues; early-stage cancers show higher mtDNAcns, while advanced stages may show depletion
Metabolic disorders[4,15,80-83]	Reflects mitochondrial dysfunction	mtDNAcn dysregulated in diabetes and other metabolic syndromes, indicating stress or compensation mechanisms	Biomarker for mitochondrial stress in diabetes; changes in mtDNAcn can indicate early disease onset or progression
Aging[47-49,55,56]	Associated with age-related cellular dysfunction	Decline in mtDNAcn in various tissues (e.g., blood, muscle) with age; some tissues exhibit increased mtDNA	Low mtDNAcn linked with poor health outcomes in aging populations, including cognitive and physical decline
Inherited mitochondrial disorders[82-93]	Indicates heteroplasmy levels and disease severity	Variations in mtDNAcn linked to phenotypes like MELAS, Pearson’s syndrome, and Leber’s hereditary optic neuropathy	High mtDNAcn linked to milder phenotypes; can guide prognosis and therapy for conditions like Kearns-Sayre syndrome and mitochondrial encephalopathy

mtDNAcn: Mitochondrial DNA copy number; AD: Alzheimer’s disease; MELAS: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; CSF: Cerebrospinal fluid.