Mitochondrial Dysfunction in Acute Kidney Injury: Intersections Between Chemotherapy and Novel Cancer Immunotherapies

Area of Science:

• Nephrology
• Immunology
• Mitochondrial Biology

Background:

• Acute kidney injury (AKI) presents significant clinical challenges with limited treatments.
• Mitochondria are increasingly recognized as central regulators of metabolic and immune responses in renal injury.
• Mitochondrial dysfunction contributes to AKI pathogenesis through inflammatory signaling and altered immune cell metabolism.

Purpose of the Study:

• To review the role of mitochondrial dysfunction in AKI, focusing on chemotherapy and immunotherapy.
• To discuss emerging mitochondrial-targeted therapeutic strategies for AKI.
• To provide a translational outlook by integrating preclinical and clinical data.

Main Methods:

• Literature review of established knowledge on mitochondrial dysfunction in AKI.
• Emphasis on mechanistic pathways activated by chemotherapy and immunotherapy.
• Discussion of emerging mitochondrial-targeted therapies and clinical trial data.

Main Results:

• Mitochondria actively participate in inflammatory signaling during AKI via DAMP release and pathway activation (e.g., TLR9, cGAS-STING, NLRP3).
• Immune cell metabolic shifts influence AKI progression or resolution.
• Immunotherapies can impact mitochondrial integrity and renal injury susceptibility.

Conclusions:

• Mitochondrial dysfunction is a critical factor in AKI development and progression.
• Mitochondrial-targeted therapies represent a promising avenue for AKI treatment.
• Further research integrating preclinical and clinical data is crucial for therapeutic advancement.