Abstract：
Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, the limited and expensive options for treating renal fibrosis place a heavy financial burden on patients and healthcare systems. Therefore, it is significant to find an effective treatment for renal fibrosis. Ferroptosis, a non-traditional form of cell death, has been found to play an important role in acute kidney injury (AKI), tumours, neurodegenerative diseases, and so on. Moreover, a growing body of research suggests that ferroptosis might be a potential target of renal fibrosis. Meanwhile, mitophagy is a type of selective autophagy that can selectively degrade damaged or dysfunctional mitochondria as a form of mitochondrial quality control, reducing the production of reactive oxygen species (ROS), the accumulation of which is the main cause of renal fibrosis. Additionally, as a receptor of mitophagy, NIX can release beclin1 to induce mitophagy, which can also bind to solute carrier family 7 member 11 (SLC7A11) to block the activity of cystine/glutamate antitransporter (system Xc-) and inhibit ferroptosis, thereby suggesting a link between mitophagy and ferroptosis. However, there have been only limited studies on the relationship among mitophagy, ferroptosis and renal fibrosis. In this paper, we review the mechanisms of mitophagy, and describe how ferroptosis and mitophagy are related to renal fibrosis in an effort to identify potential novel targets for the treatment of renal fibrosis.
摘要：
肾纤维化,以肾小球硬化和肾小管间质纤维化为特征，是慢性肾病(CKD)进展为终末期肾病(ESRD)的典型病理改变。然而,治疗肾纤维化的有限和昂贵的选择给患者和医疗保健系统带来了沉重的经济负担。因此,寻找有效的肾纤维化治疗方法具有重要意义。Ferroptosis,一种非传统的细胞死亡形式，已发现在急性肾损伤（AKI）中起重要作用，肿瘤,神经退行性疾病，等等。此外，越来越多的研究表明，铁中毒可能是肾纤维化的潜在靶点。同时,线粒体自噬是一种选择性自噬，可以选择性地降解受损或功能失调的线粒体，作为线粒体质量控制的一种形式，减少活性氧（ROS）的产生，其积累是肾脏纤维化的主要原因。此外,作为线粒体自噬的受体，NIX可以释放beclin1诱导线粒体自噬，它还可以与溶质载体家族7成员11（SLC7A11）结合，以阻断胱氨酸/谷氨酸反转运蛋白（systemXc-）的活性并抑制铁凋亡，从而表明有丝分裂和铁性凋亡之间的联系。然而,关于线粒体自噬之间的关系只有有限的研究，铁性凋亡和肾纤维化。在本文中,我们回顾了线粒体自噬的机制，并描述了铁凋亡和线粒体自噬如何与肾纤维化相关，以努力确定治疗肾纤维化的潜在新靶点。
