Mitochondrial redox imbalance in triggering regulated cell death in kidney diseases

Mitochondrial reactive oxygen species (mtROS) are critical signaling mediators that maintain renal cell viability and physiological activity, participating in antimicrobial immunity, autophagy, and oxidative stress responses. However, imbalance between mtROS production and antioxidant defenses leads to mtROS accumulation, and the excessive accumulation of mtROS disrupts cellular homeostasis by inducing key signal molecules and oxidizing specific redox-sensitive cellular macromolecules (DNA, proteins, and lipids), causing oxidative stress. This stress can trigger diverse forms of regulated cell death (RCD) in the kidneys, including autophagy, apoptosis, pyroptosis, ferroptosis, necroptosis, cuproptosis, and PANoptosis, each with distinct genetic and biochemical features. Understanding oxidative cell death in the kidney informs the development of mtROS-targeted therapeutics for kidney disorders. This review provides a concise overview on the role of mitochondrial redox imbalance in initiating various types of RCD in kidney diseases, aiming to improve the understanding of cell death mechanisms and provide new insights for disease treatment.