Mitochondrial quality control in kidney injury and repair

Abstract

Mitochondria are essential for the activity, function and viability of eukaryotic cells and mitochondrial dysfunction is involved in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease, as well as in abnormal kidney repair after AKI. Multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis, have evolved to preserve mitochondrial homeostasis under physiological and pathological conditions. Loss of these mechanisms may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and, potentially, organ failure. Accumulating evidence suggests a role of disturbances in mitochondrial quality control in the pathogenesis of AKI, incomplete or maladaptive kidney repair and chronic kidney disease. Moreover, specific interventions that target mitochondrial quality control mechanisms to preserve and restore mitochondrial function have emerged as promising therapeutic strategies to prevent and treat kidney injury and accelerate kidney repair. However, clinical translation of these findings is challenging owing to potential adverse effects, unclear mechanisms of action and a lack of knowledge of the specific roles and regulation of mitochondrial quality control mechanisms in kidney resident and circulating cell types during injury and repair of the kidney. Mitochondrial dysfunction has roles in acute kidney injury, chronic kidney disease and abnormal kidney repair. Here, the authors discuss the role of mitochondrial quality control mechanisms in kidney injury and repair and highlight their potential as therapeutic targets. Mitochondria are essential for cell viability but are highly susceptible to injury or damage. Mitochondrial homeostasis depends on multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis. Loss of mitochondrial quality control may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and possible organ failure. Acute kidney injury (AKI) is characterized by sublethal and lethal damage to kidney tubules and incomplete or maladaptive kidney repair after AKI leads to kidney fibrosis and eventually chronic kidney disease (CKD). Mitochondrial dysfunction has a critical role in the pathogenesis of AKI, abnormal kidney repair and CKD. Modulation of mitochondrial quality control is a promising therapeutic approach to preventing and treating AKI and CKD and to accelerating kidney repair. Mitochondria are essential for cell viability but are highly susceptible to injury or damage. Mitochondrial homeostasis depends on multiple quality control mechanisms, including antioxidant defence, protein quality control, mitochondrial DNA repair, mitochondrial dynamics, mitophagy and mitochondrial biogenesis. Loss of mitochondrial quality control may induce mitochondrial damage and dysfunction, leading to cell death, tissue injury and possible organ failure. Acute kidney injury (AKI) is characterized by sublethal and lethal damage to kidney tubules and incomplete or maladaptive kidney repair after AKI leads to kidney fibrosis and eventually chronic kidney disease (CKD). Mitochondrial dysfunction has a critical role in the pathogenesis of AKI, abnormal kidney repair and CKD. Modulation of mitochondrial quality control is a promising therapeutic approach to preventing and treating AKI and CKD and to accelerating kidney repair.