The Mitochondrion: A Promising Target for Kidney Disease

Mitochondrial dysfunction is important in the pathogenesis of various kidney diseases and the mitochondria potentially serve as therapeutic targets necessitating further investigation. Alterations in mitochondrial biogenesis, imbalance between fusion and fission processes leading to mitochondrial fragmentation, oxidative stress, release of cytochrome c and mitochondrial DNA resulting in apoptosis, mitophagy, and defects in energy metabolism are the key pathophysiological mechanisms underlying the role of mitochondrial dysfunction in kidney diseases. Currently, various strategies target the mitochondria to improve kidney function and kidney treatment. The agents used in these strategies can be classified as biogenesis activators, fission inhibitors, antioxidants, mPTP inhibitors, and agents which enhance mitophagy and cardiolipin-protective drugs. Several glucose-lowering drugs, such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors are also known to have influences on these mechanisms. In this review, we delineate the role of mitochondrial dysfunction in kidney disease, the current mitochondria-targeting treatment options affecting the kidneys and the future role of mitochondria in kidney pathology.

Automated summary

Mitochondrial dysfunction plays a significant role in the pathogenesis of kidney diseases and potential therapeutic interventions targeting mitochondria are under investigation. Key mechanisms underlying mitochondrial dysfunction in kidney diseases include alterations in mitochondrial biogenesis, imbalance in fusion and fission processes leading to fragmentation, oxidative stress, apoptosis caused by release of cytochrome c and mitochondrial DNA, mitophagy, and defects in energy metabolism. Current strategies focus on improving kidney function by targeting mitochondria using agents that activate biogenesis, inhibit fission, act as antioxidants, inhibit mitochondrial permeability transition pore (mPTP), enhance mitophagy, and protect cardiolipin. Glucose-lowering drugs such as glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors also have effects on these mechanisms. This review discusses the role of mitochondrial dysfunction in kidney diseases, current mitochondria-targeting treatment options, and the future possibilities of mitochondria in kidney pathology.