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

## TL;DR

This paper explores how mitochondrial dysfunction contributes to kidney injury and how cancer treatments like chemotherapy and immunotherapy affect this process.

## Contribution

The paper provides a comprehensive review of mitochondrial mechanisms in AKI and their intersections with cancer therapies.

## Key findings

- Mitochondria play a central role in both metabolic and immune responses during acute kidney injury.
- Cancer therapies can alter mitochondrial integrity, influencing kidney injury susceptibility.
- Emerging mitochondrial-targeted therapies show promise based on preclinical and clinical data.

## Abstract

Acute kidney injury (AKI) remains a major clinical challenge, with high morbidity and limited therapeutic options. In recent years, mitochondria have gained considerable attention as key regulators of the metabolic and immune responses during renal injury. Beyond their classical role in ATP production, mitochondria participate directly in inflammatory signaling, releasing mitochondrial DNA and other DAMPs that activate pathways such as TLR9, cGAS–STING, and the NLRP3 inflammasome. At the same time, immune cells recruited to the kidney undergo significant metabolic shifts that influence whether injury progresses or resolves. Increasing evidence also shows that immune-modulating therapies, including immune checkpoint inhibitors and innovative cell-based immunotherapies, can influence mitochondrial integrity, thereby altering renal susceptibility to injury. This review first summarizes the established knowledge on mitochondrial dysfunction in AKI, with emphasis on distinct mechanistic pathways activated by chemotherapy and immunotherapy. It then discusses emerging mitochondrial-targeted therapeutic strategies, logically integrating preclinical insights with data from ongoing and proposed clinical trials to present a coherent translational outlook.