Oxidative Stress and Mitochondrial Dysfunction: Molecular Interplay, Disease Mechanisms, Biomarkers, and Emerging Therapeutic Strategies: A Comprehensive Review

Ahmed Abdulsalam Abdulkader 1, * and Ali Mohammed Hussein 2

1 College of pharmacy, Ninevah University, Iraq.
2 Department of Chemistry, College of Science, University of Kirkuk, Kirkuk, Iraq.
* Corresponding Author
 
Review
World Journal of Chemical and Pharmaceutical Sciences, 2026, 09(01), 060–073.
Article DOI: 10.53346/wjcps.2026.9.1.0028
Publication history: 
Received on 27 July 2026; revised on 07 September 2026; accepted on 09 September 2026
 
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.
 
Keywords: 
Oxidative Stress; Mitochondrial Dysfunction; Reactive Oxygen Species; Redox Signaling; Bioenergetics; Antioxidants
 
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Copyright information: 
Copyright © 2026 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0