MitoNEET通过调控线粒体形态和功能减轻肾脏缺血再灌注损伤的作用及机制研究

缺血再灌注损伤（IRI）在器官移植领域不可避免，是影响器官功能和移植能否成功的关键因素，目前仍缺乏有效的防治方案。IRI肾脏中的铁代谢紊乱且线粒体形态和功能异常，线粒体外膜蛋白mitoNEET具有转运铁硫簇的功能，但对线粒体形态的影响及调控机制仍然未知。我们前期工作显示mitoNEET在发生IRI的肾脏中显著低表达，而敲低细胞中的mitoNEET会使线粒体呈过度分裂的形态，过表达mitoNEET能够降低细胞在缺氧/复氧刺激后的死亡率。由此我们推测：mitoNEET在调控线粒体的形态和功能中发挥重要作用，维持mitoNEET的正常表达水平能够缓解肾脏在缺血再灌注过程中造成的损伤。我们拟通过免疫共沉淀与质谱相结合的方法筛选出mitoNEET的互作蛋白，结合细胞生物学研究手段阐明其调控线粒体形态和功能的作用机制，探究靶向mitoNEET的药物对肾脏IRI小鼠的作用效果，为防治IRI提供新思路。

Ischemia reperfusion injury (IRI) is a complex pathophysiological phenomenon and inevitable in organ transplantation. How to alleviate renal IRI is the key issue to improve the long-term prognosis of renal transplantation and the existing methods and drugs still can not meet the clinical needs. Disordered iron homeostasis and renal mitochondrial dysfunction are manifested in the pathology of IRI. MitoNEET is a mitochondrial outer membrane protein that receives its [2Fe-2S] clusters from the mitochondrion and transfers them to acceptor proteins. However, whether mitoNEET regulates mitochondrial morphology is still unclear.Our previous work indicated that the mRNA levels of mitoNEET was specifically reduced in the IRI kidney. Knockdown of mitoNEET in HK-2 cells promotes mitochondria fission. And overexpression of mitoNEET can resist hypoxia/reoxygenation-induced cell death. Therefore, it was hypothesized that mitoNEET play a critical in maintaining mitochondrial morphology and function. And increased mitoNEET expression could attenuate renal IRI. We intend to use immunoprecipitation and mass spectrometry to screen out the proteins that interact with mitoNEET and regulate mitochondrial morphology. And we will then verify the cellular roles of the candidate proteins in the regulation of mitochondrial morphology and function. These results will provide new insight into the regulatory mechanism of mitoNEET in renal IRI.