粒体自噬
基因敲除
基因沉默
线粒体
肾缺血
肾
细胞生物学
化学
缺血
急性肾损伤
再灌注损伤
生物
细胞凋亡
医学
内科学
内分泌学
自噬
生物化学
基因
作者
Haoyu Shi,Hao Qi,Dongdong Xie,Jiayi Zhuang,Huiyue Qi,Yingbo Dai,Jiaqing Wu
标识
DOI:10.1016/j.freeradbiomed.2023.02.003
摘要
Acute kidney injury (AKI) is a prevalent clinical condition caused by sepsis and ischemia reperfusion (IR) injury. The principal driver of IR-induced AKI involves renal tubular structural changes triggered by the impairment of function in renal tubular cells. The target gene, Acyl-CoA Synthetase Family Member 2 (ACSF2), was retrieved from the GEO database based on high specific expression in renal tubular cells and location in mitochondria. Here, we substantiate that ACSF2 is specifically localized in the mitochondria of the renal tubular epithelium. Functionally silencing ACSF2 in HK2 cells enhanced hypoxia-reoxygenation (HR)-induced mitophagy, restored mitochondrial function and decreased the production of mitochondrial superoxide. Our study demonstrated that these effects were reversed by silencing Bcl-2 19-kDa interacting protein 3 (BNIP3), a receptor regulating mitophagy. In vivo, ACSF2 knockdown significantly enhanced IR-induced mitophagy and improved renal function in mice with IR injury. Conversely, BNIP3 knockdown inhibited mitophagy and exacerbated renal damage in ACSF2-knockdown mice with IR injury. In conclusion, our study demonstrated that inhibition of ACSF2 enhances mitophagy, restoring mitochondrial function and protects against IR-induced AKI, providing a new target and potential strategy for therapy.
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