Tiny genome with big impact: mitochondrial DNA in cardiovascular health

Yafang Yang; Jiaoyu Li; Lu Qian; Yuyan Xiong; Yi Yu

doi:10.1016/j.jgg.2025.12.009

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Tiny genome with big impact: mitochondrial DNA in cardiovascular health

doi: 10.1016/j.jgg.2025.12.009

a. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, Shaanxi 710069, China;
b. Xi'an Mental Health Center, Xi'an, Shaanxi 710100, China;
c. Xi'an Key Laboratory of Metabolic Disease Imaging, Xi'an No.3 Hospital, Affiliated Hospital of Northwest University, Xi'an, Shaanxi 710018, China;
d. School of Medicine, Northwest University, Xi'an, Shaanxi 710069, China

Funds:

This study was supported by grants from the National Natural Science Foundation of China (82570479), Natural Science Foundation of Shaanxi Province (2025JC-YBMS-880), Social Development Special Fund of Yunnan Province Science and Technology Department (202403AC100017), the Innovation Capability Support Plan-Medical Research Project of Xi’an Science and Technology Bureau (23YXYJ0001), and the Key Research and Development Project of the Tibet Autonomous Region (XZ202501ZY0044).

Received Date: 2025-08-07
Accepted Date: 2025-12-22
Rev Recd Date: 2025-12-15

Available Online: 2025-12-30

Abstract

Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide. Mitochondrion, a key cellular organelle, harbors its own mitochondrial DNA (mtDNA) fundamental to cellular energy production through oxidative phosphorylation (OXPHOS). Beyond its canonical bioenergetic function, mtDNA integrity, copy number, and genetic variation play critical roles in maintaining cardiovascular function. This review provides a comprehensive overview of the multifaceted contributions of mtDNA to cardiovascular health and disease. We summarize the structural features and core biological functions of mtDNA, as well as the regulatory mechanisms governing its replication, biogenesis, and turnover. Particular emphasis is focused on mtDNA abnormalities, including point mutations, large-scale deletions, copy number alterations, and epigenetic modifications, and how these disturbances drive key pathogenic processes such as oxidative stress, chronic inflammation, apoptosis, and cellular senescence within the cardiovascular system. Furthermore, we highlight accumulating evidence linking mtDNA dysregulation to major cardiovascular disorders, including heart failure, atherosclerosis, and hypertension. Finally, we discuss the emerging diagnostic potential of circulating cell-free mtDNA and related mtDNA-derived metrics as non-invasive biomarkers, and outline therapeutic strategies aimed at preserving mtDNA integrity, modulating mtDNA content, or applying gene-based interventions to mitigate cardiovascular pathology.
- Mitochondrial DNA,
- cardiovascular diseases,
- mitochondrial dysfunction,
- inflammation,
- oxidative stress,
- diagnosis and therapy

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References

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