Mitochondria: Key Target for Treating Kidney Ischemia-Reperfusion Injury

The kidney is a vital organ with high mitochondrial content, crucial for ATP production and maintaining renal function. Mitochondrial dysfunction is implicated in various renal pathologies, including ischemia-reperfusion injury (IRI), a major cause of acute kidney injury (AKI). This review systematically appraises how mitochondria serve as actionable therapeutic targets in IRI-AKI.

This review found that mitochondrial dysfunction is a central driver of renal ischemia-reperfusion injury (IRI), characterized by ATP depletion, calcium overload, and mitochondrial reactive oxygen species (mtROS) surges upon reperfusion. These events lead to mitochondrial membrane potential (ΔΨm) collapse and pathological mitochondrial permeability transition pore (mPTP) opening, ultimately causing cell death and sterile inflammation. The collective evidence strongly supports that preserving mitochondrial integrity and function, particularly by inhibiting mPTP opening and mitigating mtROS, significantly improves outcomes in preclinical models of IRI-AKI. The review highlighted various therapeutic strategies, demonstrating that interventions targeting mitochondrial dynamics, biogenesis, and quality control can offer substantial protection against IRI. Preclinical studies consistently show significant reductions in kidney injury markers and marked improvements in renal function following such interventions compared to untreated controls.