From Physiology to Pathology: The Role of Mitochondria in Acute Kidney Injuries and Chronic Kidney Diseases
Lingge Zhang, Mengqiu Miao, Xinyue Xu, Mi Bai, Mengqiu Wu, Aihua Zhang
Abstract
Background: Renal diseases remain an increasing public health issue affecting millions of people. The kidney is a highly energetic organ that is rich in mitochondria. Numerous studies have demonstrated the important role of mitochondria in maintaining normal kidney function and in the pathogenesis of various renal diseases, including acute kidney injuries (AKIs) and chronic kidney diseases (CKDs). Summary: Under physiological conditions, fine-tuning mitochondrial energy balance, mitochondrial dynamics (fission and fusion processes), mitophagy, and biogenesis maintain mitochondrial fitness. While under AKI and CKD conditions, disruption of mitochondrial energy metabolism leads to increased oxidative stress. In addition, mitochondrial dynamics shift to excessive mitochondrial fission, mitochondrial autophagy is impaired, and mitochondrial biogenesis is also compromised. These mitochondrial injuries regulate renal cellular functions either directly or indirectly. Mitochondria-targeted approaches, containing genetic (microRNAs) and pharmaceutical methods (mitochondria-targeting antioxidants, mitochondrial permeability pore inhibitors, mitochondrial fission inhibitors, and biogenesis activators), are emerging as important therapeutic strategies for AKIs and CKDs. Key Messages: Mitochondria play a critical role in the pathogenesis of AKIs and CKDs. This review provides an updated overview of mitochondrial homeostasis under physiological conditions and the involvement of mitochondrial dysfunction in renal diseases. Finally, we summarize the current status of mitochondria-targeted strategies in attenuating renal diseases.