# Mitochondria in Renal Ischemia–Reperfusion Injury: From Mechanisms to Therapeutics

## TL;DR

This paper explores how mitochondria contribute to kidney injury during ischemia and reperfusion, and reviews potential therapies targeting mitochondrial dysfunction.

## Contribution

The paper provides a comprehensive review of recent advances in understanding mitochondrial mechanisms in renal IRI and highlights mitochondria-targeted therapeutic strategies.

## Key findings

- Mitochondrial dysfunction during ischemia and reperfusion leads to ATP depletion, Ca2+ overload, and mtROS production.
- Therapeutic strategies targeting mitochondrial quality control and mtDAMP signaling are promising for treating AKI.
- Recent studies emphasize the role of mitochondrial bioenergetics and immune signaling in IRI-AKI pathogenesis.

## Abstract

Renal ischemia–reperfusion injury (IRI) is a leading trigger of acute kidney injury (AKI), a syndrome with high incidence and mortality worldwide. The kidney is among the most energy-demanding organs; its mitochondrial content is second only to the heart, rendering renal function highly contingent on mitochondrial integrity. Accumulating evidence places mitochondria at the center of IRI pathogenesis. During ischemia, ATP depletion, ionic disequilibrium, and Ca2+ overload set the stage for injury; upon reperfusion, a burst of mitochondrial reactive oxygen species (mtROS), collapse of the mitochondrial membrane potential (ΔΨm), aberrant opening of the mitochondrial permeability transition pore (mPTP), mitochondrial DNA (mtDNA) damage, and release of mitochondrial damage-associated molecular patterns (mtDAMPs) further amplify inflammation and drive regulated cell-death programs. In recent years, the centrality of mitochondrial bioenergetics, quality control, and immune signaling in IRI-AKI has been increasingly recognized. Building on advances from the past five years, this review synthesizes mechanistic insights into mitochondrial dysfunction in renal IRI and surveys mitochondria-targeted therapeutic strategies—including antioxidant defenses, reinforcement of mitochondrial quality control (biogenesis, dynamics, mitophagy), and modulation of mtDAMP sensing—with the aim of informing future translational efforts in AKI.