Aug 2026· Cellular Signalling· Vol 148, pp.
112854
· 0 citations· 123 references
Medicine
TL;DR
Evidence showing that TFAM upregulation, whether through pharmacological interventions or genetic manipulation, consistently protects against tubular cell injury, preserves mitochondrial function, and attenuates inflammation across diverse AKI models is integrated.
Abstract
Acute kidney injury (AKI) is a clinically significant syndrome characterized by rapid deterioration of renal function. Despite its complex and multifactorial pathogenesis, effective targeted therapies remain scarce. Mitochondrial dysfunction is increasingly recognized as a central driver of AKI progression. Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein that governs mitochondrial DNA (mtDNA) maintenance, transcription and replication, plays an essential role in preserving mitochondrial integrity and biogenesis. This review systematically synthesizes current knowledge on TFAM biology, with a focus on its structural features, regulatory networks, and dynamic changes in the context of AKI. We integrate evidence showing that TFAM upregulation, whether through pharmacological interventions or genetic manipulation, consistently protects against tubular cell injury, preserves mitochondrial function, and attenuates inflammation across diverse AKI models. By providing a conceptual framework that links TFAM's molecular functions to its pathophysiological roles in the kidney, this review highlights TFAM as a promising therapeutic node. We also identify key knowledge gaps and propose future research directions to facilitate the translation of TFAM-targeted strategies into clinical practice.
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.
Ziqiang Chen, Yunhe Wang, Yijing Li et al.· Molecular Medicine Reports· 0 citations
Acute kidney injury (AKI) is a major global health challenge associated with substantial morbidity, mortality, and progression to chronic kidney disease. Increasing evidence indicates that oxidative stress, mitochondrial dysfunction, inflammatory signaling, regulated cell death, and maladaptive tissue repair play central roles in AKI pathogenesis, yet effective disease-modifying pharmacological therapies remain unavailable. This narrative review critically evaluated current evidence regarding the pharmacological characteristics, molecular mechanisms, and translational potential of alpha-mangostin (AM), the principal prenylated xanthone isolated from the pericarp of Garcinia mangostana L., through a comprehensive synthesis of experimental and mechanistic studies. Available preclinical evidence consistently demonstrates that AM improves renal function and attenuates histopathological injury, particularly in cisplatin-induced nephrotoxicity and glycerol-induced rhabdomyolysis models. These renoprotective effects are primarily associated with suppression of oxidative stress, activation of the Nrf2/HO-1 antioxidant pathway, inhibition of NF-κB-mediated inflammatory signaling, preservation of mitochondrial function, and attenuation of apoptosis. Several emerging pathways may also contribute to AM-mediated renoprotective effects; however, current evidence remains indirect, and their roles require validation in kidney-specific models. Clinical translation remains limited by poor oral bioavailability, insufficient pharmacokinetic data, lack of standardized formulations, and the absence of human clinical trials. Overall, current evidence suggests that AM has preliminary renoprotective potential in experimental AKI models. However, the limited number of available studies, predominance of cisplatin-induced nephrotoxicity models, insufficient pharmacokinetic and safety data, and absence of human clinical studies preclude conclusions regarding its clinical efficacy or translational readiness. Further validation in diverse and clinically relevant AKI models is required before clinical investigation can be considered.
Atthaphong Phongphithakchai, Nawanwat C. Pattaranggoon, Kraiyasak Wongna et al.· Antioxidants· 0 citations
In renal cell carcinoma (RCC), alterations in cellular metabolism are a defining feature, among which impaired mitochondrial function stands out as a key factor influencing both tumor aggressiveness and patient responses to therapy. The aim of this review is to systematically synthesize current knowledge on the role of mitochondrial dysfunction in RCC pathogenesis and to explore emerging therapeutic strategies targeting mitochondrial vulnerabilities. This comprehensive analysis examines the integrated dysregulation of core mitochondrial processes—bioenergetic metabolism, organelle dynamics, programmed cell death pathways, redox homeostasis, and selective autophagy—in driving RCC pathogenesis. Our synthesis reveals how genetic drivers, molecular regulators, and microenvironmental cues converge to remodel mitochondrial function, creating both adaptive advantages and therapeutic vulnerabilities. A paradoxical duality emerges in mitochondrial biology: processes such as fission, mitophagy, and reactive oxygen species (ROS) generation can simultaneously support tumor adaptation while rendering cells susceptible to targeted interventions. We evaluate emerging therapeutic approaches directed at mitochondrial vulnerabilities, including metabolic inhibitors, nanoscale delivery systems, and phytochemical agents, while addressing current limitations in specificity and resistance mechanisms. Based on current preclinical evidence, this integrated perspective establishes mitochondrial dysfunction as a central determinant of RCC malignancy and suggests potential combinatorial strategies for precision oncology approaches that warrant further investigation.
Overall, redox-mediated mitochondrial injury represents a shared pathogenic axis and a potential therapeutic target across kidney diseases, and emerging biomarkers and therapeutic strategies targeting oxidative stress and mitochondrial dysfunction are discussed.
Ewelina Młynarska, K. Bojdo, Katarzyna Hossa et al.· Biomolecules· 0 citations
Given the multifactorial nature of DCM, combination therapies targeting ferroptosis and mitochondrial dysfunction may offer superior outcomes, and future drug development should prioritize agents that precisely regulate these interrelated pathways, enabling personalized treatment strategies for DCM.
Yiting Tang, Qian Wu, Yu-Peng Chen et al.· World Journal of Diabetes· 0 citations
This review focuses on the core mechanisms that link mitochondrial dysfunction to disease progression and the major barriers to translation, and examines biomarker development and the major barriers to translation.
L. Elabbasy· Current opinion in pharmacol...· 0 citations
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