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...
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...
Ferroptosis suppressor protein 1, CoQ10, CoQ10H2, and intracellular NADH levels in HK-2 cells were assessed by Western blot, ELISA kit, and NAD/NADH kit. NAD+/NADH ratio was also calculated, and 4-Hydroxynonal fluorescence intensity was assessed by immunofluorescence. HK-2 cell viability and...
and they were then treated with ginsenoside Rg1 and ferroptosis suppressor protein 1 inhibitor. Ferroptosis suppressor protein 1, CoQ10, CoQ10H2, and intracellular NADH levels in HK-2 cells were assessed by Western blot, ELISA
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...
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...
Recently, two teams of Doll and Bersuker found that it plays a role in inhibiting ferroptosis in the plasma membrane through the NADPH-FSP1-CoQ10 pathway, and this pathway has a parallel effect with glutathione (GSH)/GPX4 (glutathione peroxidase 4) ferroptosis inhibition axis [13], [14], ...
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 ...
Recently, two teams of Doll and Bersuker found that it plays a role in inhibiting ferroptosis in the plasma membrane through the NADPH-FSP1-CoQ10 pathway, and this pathway has a parallel effect with glutathione (GSH)/GPX4 (glutathione peroxidase 4) ferroptosis inhibition axis [13], [14], ...
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...