Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster.
Fasting, but Not Aging, Dramatically Alters the Redox Status of Cysteine Residues on Proteins in Drosophila melanogaster.
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DOI：
10.1016/j.celrep.2015.05.033
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发表时间：
2015-06-30
期刊：
影响因子：
8.8
通讯作者：
Murphy MP
中科院分区：
文献类型：
--
作者：
Menger KE;James AM;Cochemé HM;Harbour ME;Chouchani ET;Ding S;Fearnley IM;Partridge L;Murphy MP
改变蛋白质表面半胱氨酸残基的氧化还原状态是对环境挑战的重要响应。虽然衰老和禁食改变了许多氧化还原过程，但半胱氨酸残基的作用尚不确定。为了解决这一问题，我们使用氧化还原蛋白质组学技术，氧化同位素编码的亲和标签（OxICAT），以评估半胱氨酸残基氧化还原在果蝇衰老和禁食期间的变化。这种方法使我们能够同时识别和定量的氧化还原状态的几百个半胱氨酸残基在体内。半胱氨酸残基在幼蝇体内呈双峰分布，峰值在可逆氧化的10%和85%。令人惊讶的是，这些半胱氨酸残基并没有随着年龄的增长而变得更加氧化。相比之下，禁食24小时显著氧化在进食条件下还原的半胱氨酸残基，同时还还原最初氧化的半胱氨酸残基。我们的结论是禁食，而不是老化，显着改变半胱氨酸残基的氧化还原状态在果蝇。果蝇中半胱氨酸残基的氧化还原状态和身份可以通过OxICAT来确定。总体上，半胱氨酸残基的氧化还原状态不随年龄而改变。H2O2和百草枯对半胱氨酸残基的氧化还原状态具有令人惊讶的明显影响。禁食24小时显著改变了半胱氨酸残基的氧化还原状态。Menger等人测量了黑腹果蝇在衰老和禁食过程中半胱氨酸残基的氧化还原变化。令人惊讶的是，老化对半胱氨酸残基的氧化还原状态没有影响。与此相反，禁食显着影响半胱氨酸残基，表明半胱氨酸残基氧化还原状态在禁食中的作用。
Altering the redox state of cysteine residues on protein surfaces is an important response to environmental challenges. Although aging and fasting alter many redox processes, the role of cysteine residues is uncertain. To address this, we used a redox proteomic technique, oxidative isotope-coded affinity tags (OxICAT), to assess cysteine-residue redox changes in Drosophila melanogaster during aging and fasting. This approach enabled us to simultaneously identify and quantify the redox state of several hundred cysteine residues in vivo. Cysteine residues within young flies had a bimodal distribution with peaks at ∼10% and ∼85% reversibly oxidized. Surprisingly, these cysteine residues did not become more oxidized with age. In contrast, 24 hr of fasting dramatically oxidized cysteine residues that were reduced under fed conditions while also reducing cysteine residues that were initially oxidized. We conclude that fasting, but not aging, dramatically alters cysteine-residue redox status in D. melanogaster. The redox state and identity of cysteine residues in flies can be determined by OxICAT Overall cysteine-residue redox state does not change with age H2O2 and paraquat have surprisingly distinct effects on cysteine-residue redox state Fasting for 24 hr dramatically alters the redox state of cysteine residues Using a redox proteomic mass spectrometry technique, oxidative isotope-coded affinity tags (OxICAT), Menger et al measured cysteine residue redox changes in Drosophila melanogaster during aging and fasting. Surprisingly, aging had no impact on cysteine-residue redox state. In contrast, fasting dramatically affected cysteine residues, suggesting a role for cysteine-residue redox status in fasting.