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

Table 5 Comparison of techniques for modulating mtDNA copy number therapeutic strategy

Therapeutic strategy	Mechanism	Applications	Advantages	Challenges
AMPK activation	Enhances mitochondrial biogenesis via PGC-1α activation	Neurodegenerative diseases, aging	Promotes energy balance	Off-target effects, limited clinical trials
Genome editing tools	Targets mtDNA mutations or modulates copy number	Mitochondrial diseases, cancer therapy	Precision targeting	Ethical concerns, technical challenges
Autophagy induction	Removes damaged mitochondria	Improves mitochondrial quality	Enhances cellular health	Excessive clearance may have long-term side effects
Small molecules and vitamins	Increases mtDNAcn	Metabolic and neurodegenerative disorders	Cost-effective	Limited understanding of long-term effects

AMPK; Adenosine monophosphate-activated protein kinase; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; mtDNA: Mitochondrial DNA; mtDNAcn: Mitochondrial DNA copy number.