Loss of tafazzin in yeast leads to increased oxidative stress during respiratory growth
Loss of tafazzin in yeast leads to increased oxidative stress during respiratory growth
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DOI：
10.1111/j.1365-2958.2008.06216.x
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Greenberg, Miriam L.
中科院分区：
文献类型：
--
作者：
Chen, Shuliang;He, Quan;Greenberg, Miriam L.
Tafazzin(TAZ)基因从酵母到人类都是高度保守的，酵母taz1缺失突变体表现出心磷脂(CL)代谢的变化、线粒体功能障碍和超复合体的稳定，类似于Barth综合征，Barth综合征是一种由于丢失Tafazzin而引起的人类疾病。我们先前已经证明酵母Tafazzin突变体taz1 Delta不能重塑CL，在高温下对乙醇敏感。在目前的报道中，我们发现CL突变体taz1 Delta和crd1 Delta不能合成CL，但它们对乙醇的反应表现为蛋白质羰基化增加，这是活性氧物种(ROS)的指标。ROS的增加很可能不是由于氧化防御系统的缺陷，因为CL突变体对百草枯、甲苯二酮或过氧化氢(H_2O_2)不敏感。补充油酸可以挽救taz1 Delta突变体中的乙醇敏感性和增加的蛋白质羰基化，但在crd1 Delta中不能，这表明油酰CL和/或油酰单体CL能够通过减少氧化应激而使taz1 Delta在乙醇中生长。我们发现taz1 Delta突变体在呼吸生长过程中氧化应激增加，这可能对理解Barth综合征的发病机制有重要意义。
The tafazzin (TAZ) gene is highly conserved from yeast to humans, and the yeast taz1 null mutant shows alterations in cardiolipin (CL) metabolism, mitochondrial dysfunction and stabilization of supercomplexes similar to those found in Barth syndrome, a human disorder resulting from loss of tafazzin. We have previously shown that the yeast tafazzin mutant taz1 Delta, which cannot remodel CL, is ethanol-sensitive at elevated temperature. In the current report, we show that in response to ethanol, CL mutants taz1 Delta as well as crd1 Delta, which cannot synthesize CL, exhibited increased protein carbonylation, an indicator of reactive oxygen species (ROS). The increase in ROS is most likely not due to defective oxidant defence systems, as the CL mutants do not display sensitivity to paraquat, menadione or hydrogen peroxide (H2O2). Ethanol sensitivity and increased protein carbonylation in the taz1 Delta mutant but not in crd1 Delta can be rescued by supplementation with oleic acid, suggesting that oleoyl-CL and/or oleoyl-monolyso-CL enables growth of taz1 Delta in ethanol by decreasing oxidative stress. Our findings of increased oxidative stress in the taz1 Delta mutant during respiratory growth may have important implications for understanding the pathogenesis of Barth syndrome.