Redox-Mediated Mitochondrial Dysfunction as a Common Pathogenic Axis in Acute Kidney Injury and Chronic Kidney Disease

Oxidative Stress and Mitochondrial Dysfunction in Chronic Kidney Disease: From Molecular Mechanisms to Biomarkers and Targeted Therapies

Chronic kidney disease (CKD) represents a major global health challenge, affecting more than 10% of the population and contributing substantially to morbidity and premature mortality. Growing evidence identifies oxidative stress and mitochondrial dysfunction as central drivers of renal injury and disease progression across diverse etiologies. The kidney is one of the most mitochondria-rich organs in the body, reflecting the high bioenergetic demands required for tubular reabsorption and metabolic homeostasis. Disruption of mitochondrial oxidative phosphorylation, excessive production of reactive oxygen species (ROS), and impaired mitochondrial quality control mechanisms promote tubular injury, inflammation, and fibrosis. In particular, dysfunction of the electron transport chain, activation of NADPH oxidase isoforms—especially NOX4—and alterations in mitochondrial dynamics create a vicious cycle of oxidative damage and bioenergetic failure. Emerging evidence highlights the importance of mitochondrial quality control pathways, including fusion–fission balance, PINK1/Parkin-mediated mitophagy, and mitochondrial biogenesis regulated by PGC-1α and TFAM. Additional mechanisms include ferroptosis, epigenetic regulation, mitochondrial DNA-mediated innate immune activation, and Na+/K+-ATPase-linked redox signaling. At the translational level, redox and mitochondrial biomarkers and targeted therapies are biologically compelling, but the evidence is uneven: most candidate biomarkers remain insufficiently standardized, and direct mitochondria-targeted interventions are supported predominantly by preclinical studies or small human proof-of-concept trials. This review therefore emphasizes not only mechanistic advances but also conflicting findings, model limitations, and the barriers that currently separate experimental efficacy from clinically meaningful CKD outcomes.

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

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.

Mitochondrial quality control in acute liver injury and its therapeutic implications (Review)

Acute liver injury (ALI) is a clinically important syndrome with limited mechanism-based therapies. Notably, mitochondrial dysfunction is increasingly recognized as a central driver of hepatocellular damage and repair failure. The present narrative review aims to summarize the current evidence on mitochondrial quality control (MQC) in ALI, with an emphasis on mitophagy, mitochondrial biogenesis, mitochondrial dynamics, etiology-specific regulation and therapeutic implications. For the present review, relevant experimental and translational studies addressing MQC-related mechanisms and interventions in major forms of ALI, including drug-induced liver injury, ischemia-reperfusion injury and viral ALI, were reviewed and integrated. The findings indicated that MQC operates as an interconnected network rather than as isolated pathways. Mitophagy, mitochondrial dynamics and mitochondrial biogenesis are temporally coordinated to remove damaged mitochondria, remodel mitochondrial networks and restore bioenergetic capacity. However, MQC responses differ across ALI etiologies, and inappropriate or excessive activation may become maladaptive. In conclusion, understanding MQC as a dynamic and context-dependent repair system may provide a conceptual basis for precision interventions in ALI. Future studies should clarify spatiotemporal MQC regulation, establish reliable biomarkers and validate MQC-targeted therapies in clinically relevant settings.

Genetic risk and telomere dynamics in chronic kidney disease associated with mitochondrial dysfunction and implications for Coenzyme Q10 therapy

Chronic kidney disease (CKD) is a major global health burden characterized by progressive loss of renal function and an increased risk of cardiovascular morbidity and mortality. The risk of adverse outcomes rises with declining glomerular filtration rate, with cardiovascular disease representing the leading cause of death in advanced CKD. In addition to traditional risk factors such as diabetes and hypertension, oxidative stress and mitochondrial dysfunction have emerged as key contributors to disease pathogenesis. Oxidative stress in CKD arises from mitochondrial dysfunction and inflammation-mediated pathways, leading to endothelial dysfunction, chronic inflammation and accelerated cellular aging. Coenzyme Q10 (CoQ10), a lipid-soluble component of the mitochondrial electron transport chain, plays a central role in cellular bioenergetics and antioxidant defense. Reduced CoQ10 levels observed in CKD contribute to impaired mitochondrial function and increased oxidative damage. Genetic variation in pathways regulating oxidative stress and CoQ10 metabolism may influence CKD susceptibility. Polymorphisms such as NQO1 rs1800566 affect the reduction of CoQ10 to its active antioxidant form and may modulate individual responses to oxidative stress. Telomere shortening, a marker of biological aging, is closely associated with oxidative stress and has been linked to CKD progression. Recent advances in genomic research have enabled the development of genetic risk scores (GRS) that integrate multiple genetic variants to predict disease susceptibility. In addition, social determinants of health (SDoH), including socioeconomic and environmental factors, significantly influence CKD outcomes through their impact on biological pathways. This review synthesizes current evidence on the interplay between mitochondrial dysfunction, telomere dynamics, genetic variation and environmental influences in CKD. The therapeutic potential of CoQ10 supplementation is also discussed. Integrating molecular, genetic and social determinants provides a comprehensive framework for understanding CKD and advancing precision medicine approaches.

[Research advances on the role of mitochondrial dysfunction and metabolic reprogramming in sepsis-associated acute kidney injury].

Remodeling lipid and mitochondrial homeostasis: a novel mechanism by which polydatin attenuates renal tubular senescence in chronic kidney disease.

PD rewires lipid metabolism, restores mitochondrial homeostasis, and activates the SIRT3/SOD2 axis to mitigate DNA damage and suppress tubular senescence, thereby halting CKD progression and position PD as a promising therapeutic candidate for senescence-associated kidney diseases.