Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Nephrology and Urology Research Institute of Wuhan University, Wuhan 430060, China.
Int J Mol Sci. 2022 Dec 2;23(23):15166. doi: 10.3390/ijms232315166.
The kidney is a mitochondria-rich organ, and kidney diseases are recognized as mitochondria-related pathologies. Intact mitochondrial DNA (mtDNA) maintains normal mitochondrial function. Mitochondrial dysfunction caused by mtDNA damage, including impaired mtDNA replication, mtDNA mutation, mtDNA leakage, and mtDNA methylation, is involved in the progression of kidney diseases. Herein, we review the roles of mtDNA damage in different setting of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). In a variety of kidney diseases, mtDNA damage is closely associated with loss of kidney function. The level of mtDNA in peripheral serum and urine also reflects the status of kidney injury. Alleviating mtDNA damage can promote the recovery of mitochondrial function by exogenous drug treatment and thus reduce kidney injury. In short, we conclude that mtDNA damage may serve as a novel biomarker for assessing kidney injury in different causes of renal dysfunction, which provides a new theoretical basis for mtDNA-targeted intervention as a therapeutic option for kidney diseases.
肾脏是一个富含线粒体的器官，肾脏疾病被认为与线粒体相关的病变有关。完整的线粒体 DNA（mtDNA）维持正常的线粒体功能。mtDNA 损伤导致的线粒体功能障碍，包括 mtDNA 复制受损、mtDNA 突变、mtDNA 渗漏和 mtDNA 甲基化，与肾脏疾病的进展有关。本文综述了 mtDNA 损伤在不同肾脏疾病中的作用，包括急性肾损伤（AKI）和慢性肾脏病（CKD）。在多种肾脏疾病中，mtDNA 损伤与肾功能丧失密切相关。外周血清和尿液中的 mtDNA 水平也反映了肾脏损伤的状态。通过外源性药物治疗减轻 mtDNA 损伤可以促进线粒体功能的恢复，从而减轻肾脏损伤。总之，我们得出结论，mtDNA 损伤可能作为评估不同原因引起的肾功能障碍的肾脏损伤的新型生物标志物，为 mtDNA 靶向干预作为肾脏疾病的治疗选择提供了新的理论依据。
