Acute kidney injury (AKI) remains a significant global health challenge, with high mortality rates and the potential for progression to chronic kidney disease. One promising avenue of intervention is targeting mitochondrial biogenesis (MB), a critical cellular process that promotes energy metabolism, stress resistance, and cell survival. By enhancing MB, it may be possible to restore mitochondrial function, alleviate oxidative stress, and improve renal recovery.

The kidneys, particularly renal tubular epithelial cells, are highly dependent on robust mitochondrial function due to their substantial energy demands. During AKI, mitochondrial dysfunction leads to decreased energy production, heightened oxidative damage, and cell death, exacerbating kidney injury. Suppressing MB not only disrupts cellular energy balance but also impairs the ability to respond to injurious stimuli, accelerating disease progression. Therefore, therapeutic strategies aimed at boosting MB could significantly mitigate AKI severity and improve patient outcomes.

Several factors regulate MB, including PGC-1α, a key transcriptional coactivator that stimulates the expression of genes involved in mitochondrial function. Activation of PGC-1α enhances ATP production, reduces reactive oxygen species (ROS), and supports cell survival during stress. Compounds like resveratrol, which activate PGC-1α via SIRT1-mediated deacetylation, have shown potential in promoting mitochondrial health. Furthermore, small molecules like ZLN005 and pyrroloquinoline quinone (PQQ) can enhance MB through pathways involving AMPK activation and CREB phosphorylation, respectively.

However, MB regulation is complex, and excessive activation may lead to protein misfolding, mitochondrial damage, and cellular toxicity. Thus, achieving a balanced activation of MB is essential to prevent unintended consequences. Advances in understanding MB signaling pathways and identifying modulatory compounds offer new therapeutic possibilities. Notably, nanotechnology-based drug delivery systems are being developed to precisely target mitochondrial dysfunction in AKI, improving therapeutic efficacy while minimizing side effects.

Translating these insights into clinical practice requires overcoming challenges related to drug specificity, targeted delivery, and patient variability. Personalized approaches that consider the etiology and subtype of AKI, as well as patient-specific factors like comorbidities, are essential for optimizing treatment. Additionally, integrating multi-omics data can help identify biomarkers predictive of treatment response, enabling more precise and effective therapies.

Mitochondria-targeted therapies hold immense potential for transforming AKI treatment. By addressing the underlying mitochondrial dysfunction, these strategies offer a pathway to enhance renal recovery, reduce disease progression, and improve patient survival. As research advances, integrating these innovative therapies into clinical protocols could revolutionize the management of AKI.

# # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 8.4
Impact Factor:9.4

# # # # # #

More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available online in ScienceDirect (https://www.sciencedirect.com/journal/genes-and-diseases ).
Submissions to Genes & Disease may be made using Editorial Manager (https://www.editorialmanager.com/gendis/default.aspx ).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.com
X (formerly Twitter): @GenesNDiseases (https://x.com/GenesNDiseases )

# # # # # #
Reference
Yajie Hao, Fahui Chen, Xiya Ren, Xiu Huang, Xiaoshuang Zhou, Harnessing mitochondrial biogenesis to combat acute kidney injury: Current insights and futuredirections, Genes & Diseases, Volume 12, Issue 6, 2025, 101645, https://doi.org/10.1016/j.gendis.2025.101645