研究最终确认FSP1是一个强效的铁死亡抑制因子,它通过肉豆蔻酰化定位于质膜,在此位置上FSP1介导NADH依赖的辅酶Q(CoQ)还原,CoQ作为抗氧化剂抑制脂质过氧化和铁死亡。此外,研究还揭示了非线粒体CoQ的基本功能是防止脂质损伤并避免铁死亡。研究结...
由于AIF家族成员已被证明具有NADH:泛醌氧化还原酶活性,我们假设FSP1通过使用NAD(P)H再生亲脂性自由基捕获抗氧化剂来抑制pLPO。还原形式的辅酶q10(coq10-h2)已被报道在磷脂和脂蛋白中是一种很好的捕获自由基的抗氧化剂,但被认为在线粒体外的重要性有限,作为一种有效的再循环机制,辅酶q10(coq10-h2)在磷脂和脂蛋...
而辅酶Q10(CoQ10)已经被证实是磷脂和脂蛋白非常好的自由基清除抗氧化剂。因此研究者大胆假设,严谨验证,通过敲除合成的关键酶CoQ10,热动力学实验(检测Km,Ki,Vmax),NADH消耗实验等证实FSP1 与CoQ10存在互作(FSP1还原CoQ10),阻止脂质过氧化...
Moreover, FSP1 has ferroptosis-related enzyme activities including NADH/NADPH dependent CoQ10 oxidoreductase [16] and vitamin K reductase [19], which reduce CoQ10 or vitamin K [phylloquinone, menaquinone-4 (MK-4) and menadione, etc.] to produce CoQ10H2, vitamin K hydroquinone (VKH2), and...
h, Oxidation of NADH by recombinant FSP1 in the presence of coenzyme Q1. Panels g and h are representative of two biological replicates, and e shows a single experiment. Source data Extended Data Fig. 8 Lipid peroxidation in CoQ-depleted cells. a, Total CoQ levels in control and FSP1KO...
Results: LPS treatment diminished ferroptosis suppressor protein 1, CoQ10, CoQ10H2, and NADH contents in HK-2 cells, while facilitating NAD+/NADH ratio and relative 4- Hydroxynonal fluorescence intensity. FSP1 overexpression inhibited lipopolysaccharideinduced lipid peroxidation in HK-2 cells via the...
从机制上讲,我们的数据支持一个模型,在该模型中,肉豆蔻酰化作用将FSP1靶向质膜,在那里它介导了依赖NADH的辅酶Q的还原,而还原性辅酶Q的功能是一种捕捉自由基的抗氧化剂,可以抑制脂质过氧化物的传播(图4H)。我们的数据还显示,非线粒体辅酶Q的一个基本作用是作为抗氧化剂发挥作用,防止脂质损伤,从而防止铁死亡。FSP...
Representative immunofluorescence images of FSP1 (green), Na+/K+-ATPase (red) and Hoechst (blue) are shown, scale bar = 10 μm. (H) NADH consumption assay (340 nm) in PBS buffer using purified FSP1 in combination with CoQ1. The striatum of mice treated with 0.625 nmol kA for 48 h...
CoQ (Fig.2d). Interestingly, the H2O2amount generated by E155A or L329S mutations was not less than that of cFSP1 wild type (Fig.5d), which may be explained by two possible reasons: (i) the H2O2amount was a cumulative result of reaction processes, consistent with the NADH oxidation ...
Curcumin Induces Ferroptosis in A549 CD133+ Cells through the GSH-GPX4 and FSP1-CoQ10-NAPH Pathways. curcumin induced ferroptosis through inhibiting the GSH-GPX4 and FSP1-CoQ10-NADH pathways in A549 CD133+ cells, resulting in the inhibition of their self... J Zhou,L Zhang,J Yan,... -...