Mutations in Complex I of the Mitochondrial Electron-Transport Chain Sensitize the Fruit Fly (Drosophila melanogaster) to Ether and Non-Ether Volatile Anesthetics.
Mutations in Complex I of the Mitochondrial Electron-Transport Chain Sensitize the Fruit Fly (Drosophila melanogaster) to Ether and Non-Ether Volatile Anesthetics.
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DOI：
10.3390/ijms24031843
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发表时间：
2023-01-17
影响因子：
5.6
通讯作者：
Perouansky, Misha
中科院分区：
文献类型：
--
作者：
Borchardt, Luke A. A.;Scharenbrock, Amanda R. R.;Olufs, Zachariah P. G.;Wassarman, David A. A.;Perouansky, Misha
关键词：
线粒体电子传递链（mETC）含有挥发性全身麻醉剂（VGAs）的分子靶点，这使得突变携带者面临麻醉并发症的风险。携带mETC Complex I核心亚基突变的果蝇ND-2360114和mt:ND2del1系复制了哺乳动物中由同源突变引起的Leigh综合征（LS）的许多特征，并可作为LS的模型。ND-2360114果蝇在暴露于异氟醚而非相关麻醉剂七氟醚后，对挥发性麻醉醚表现出行为过敏，并产生年龄和氧依赖的麻醉诱导神经毒性（AiN）表型。本文的目的是研究mETC的络合物I和络合物II-V中的烷烃挥发性麻醉氟烷和其他突变是否引起AiN。结果表明：(1)ND-2360114和mt:ND2del1对氟烷的毒性敏感；（ii）氟烷对野生型蝇在缺氧条件下具有毒性；（iii）复合体I附属亚基的等位基因易患AiN；（iv）复合物II-V的突变不会导致AiN表型。我们得出结论，AiN既不局限于乙醚麻醉剂，也不局限于复合物I核心亚基的突变。
The mitochondrial electron transport chain (mETC) contains molecular targets of volatile general anesthetics (VGAs), which places carriers of mutations at risk for anesthetic complications. The ND-2360114 and mt:ND2del1 lines of fruit flies (Drosophila melanogaster) that carry mutations in core subunits of Complex I of the mETC replicate numerous characteristics of Leigh syndrome (LS) caused by orthologous mutations in mammals and serve as models of LS. ND-2360114 flies are behaviorally hypersensitive to volatile anesthetic ethers and develop an age- and oxygen-dependent anesthetic-induced neurotoxicity (AiN) phenotype after exposure to isoflurane but not to the related anesthetic sevoflurane. The goal of this paper was to investigate whether the alkane volatile anesthetic halothane and other mutations in Complex I and in Complexes II–V of the mETC cause AiN. We found that (i) ND-2360114 and mt:ND2del1 were susceptible to toxicity from halothane; (ii) in wild-type flies, halothane was toxic under anoxic conditions; (iii) alleles of accessory subunits of Complex I predisposed to AiN; and (iv) mutations in Complexes II–V did not result in an AiN phenotype. We conclude that AiN is neither limited to ether anesthetics nor exclusive to mutations in core subunits of Complex I.
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影响因子：
4.6
作者：
Olufs, Zachariah P. G.;Loewen, Carin A.;Perouansky, Misha
通讯作者：
Perouansky, Misha
DOI：
10.1073/pnas.1006214107
发表时间：
2010-06-15
影响因子：
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影响因子：
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作者：
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通讯作者：
Perouansky, Misha
DOI：
10.1073/pnas.1215849110
发表时间：
2012-12-26
影响因子：
11.1
作者：
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通讯作者：
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