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Mitochondria: The Crossroads of Complement Activation and Kidney Injury Progression
Madison K McGraw1, Nirmala Parajuli1
1Department of Pharmacology and Toxicology, University of Arkansas for Medical Science, Little Rock, AR 72205, USA.
International Journal of Molecular Sciences
|June 26, 2026
Summary
Acute kidney injury can progress to chronic kidney disease. This review highlights how mitochondrial dysfunction and complement system activation, particularly complement 5 (C5), drive this progression and offers C5 as a potential therapeutic target.
Area of Science:
- Nephrology
- Immunology
- Mitochondrial Biology
Background:
- Acute kidney injury (AKI) is a common condition that can lead to chronic kidney disease (CKD).
- Mechanisms linking AKI to CKD, including mitochondrial dysfunction and complement system activation, are not fully understood.
- These processes are intertwined, but therapeutic targets remain limited.
Purpose of the Study:
- To review the role of mitochondria in kidney pathophysiology.
- To explore the relationship between mitochondria and the complement system, focusing on complement 5 (C5).
- To identify C5 as a potential therapeutic target for kidney disease.
Main Methods:
- Literature review of studies on AKI, CKD, mitochondrial dysfunction, and complement system activation.
- Focus on the role of terminal complement cascade components, specifically C5.
- Analysis of the interplay between mitochondrial function and complement-mediated inflammation.
Main Results:
- Mitochondrial dysfunction and complement activation are key drivers of AKI to CKD transition.
- Complement 5 (C5) significantly impacts mitochondrial function in the kidney.
- C5 produces pro-inflammatory anaphylatoxins, making it a critical factor in kidney injury.
Conclusions:
- The relationship between mitochondria and the complement system, especially C5, is crucial in kidney disease progression.
- Targeting C5 may offer a novel therapeutic strategy for mitigating kidney injury and preventing CKD.
- Further research into this interplay is warranted for clinical applications.
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