Oxidative Stress and Mitochondrial Dysfunction: Molecular Interplay, Disease Mechanisms, Biomarkers, and Emerging Therapeutic Strategies: A Comprehensive Review
TL;DR
This review discusses the biochemical links between oxidative stress and mitochondrial dysfunction and their roles in cardiovascular disease, type 2 diabetes, neurodegeneration, metabolic liver disease, cancer, and aging, and widely used biomarkers and current therapeutic strategies.
Abstract
Oxidative stress and mitochondrial dysfunction were intimately linked processes driving aging and numerous human diseases. Mitochondria generating reactive oxygen species (ROS) during energy metabolism; physiological ROS levels are vital for cell signaling and adaptation. However, excessive ROS damage mitochondrial DNA (mtDNA), respiratory proteins, and membrane lipids, reducing ATP production, disturbing calcium balance, and impairing organelle function. In turn, damaged mitochondria produce more ROS and release mtDNA, activating inflammatory pathways such as cGAS-STING and NLRP3. Mitochondrial quality control mechanisms—fusion, fission, mitophagy, proteostasis, and PGC-1α-driven biogenesis—are essential for homeostasis. This review discusses the biochemical links between oxidative stress and mitochondrial dysfunction and their roles in cardiovascular disease, type 2 diabetes, neurodegeneration, metabolic liver disease, cancer, and aging. We summarize widely used biomarkers (F2-isoprostanes, oxidized nucleic acids, mitochondrial respiration, multi-omics) and current therapeutic strategies, including exercise-induced mitohormesis, NRF2 activation, mitochondria-targeted antioxidants (MitoQ), cardiolipin-targeting peptides (elamipretide), NAD⁺ restoration, and mitophagy enhancers (urolithin A). Although several approaches show biological promise, clinical outcomes remain variable. Future therapies must prioritize restoring mitochondrial quality and redox balance over simplistic ROS scavenging.