Department of Viticulture and Oenology, Institute for Wine Biotechnology, Stellenbosch University, Matieland, South Africa.
FEMS Yeast Res. 2010 May;10(3):270-81. doi: 10.1111/j.1567-1364.2010.00610.x. Epub 2010 Jan 28.
l-Carnitine plays a well-documented role in eukaryotic energy homeostasis by acting as a shuttling molecule for activated acyl residues across intracellular membranes. This activity, supported by carnitine acyl-transferases and transporters, is referred to as the carnitine shuttle. However, several pleiotropic and often beneficial effects of carnitine in humans have been reported that appear to be unrelated to shuttling activity, but little conclusive evidence regarding molecular mechanisms exists. We have recently demonstrated a role of carnitine, independent of the carnitine shuttle, in yeast stress protection. Here, we show that carnitine specifically protects against oxidative stress caused by H(2)O(2) and the superoxide-generating agent menadione. Surprisingly, carnitine has a detrimental effect on survival when combined with thiol-modifying agents. Central elements of the oxidative stress response, specifically the transcription factors Yap1p and Skn7p, are shown to be required for carnitine's protective effect, but several downstream effectors are dispensable. A DNA microarray-based analysis identifies Cyc3p, a cytochrome c heme lyase, as being important for carnitine's impact during oxidative stress. These findings establish a direct genetic link to a carnitine-related phenotype that is independent of the shuttle system and suggests that Saccharomyces cerevisiae should provide a useful model for further elucidation of carnitine's physiological roles.
左旋肉碱在真核生物能量稳态中起着有据可查的作用，它作为一种穿梭分子，将激活的酰基残基穿过细胞内的膜。这种活性由肉碱酰基转移酶和转运蛋白支持，被称为肉碱穿梭。然而，已经报道了左旋肉碱在人体内的几种多效性且通常有益的作用，这些作用似乎与穿梭活性无关，但关于分子机制的结论性证据很少。我们最近证明了肉碱在酵母应激保护中的作用，与肉碱穿梭无关。在这里，我们表明肉碱可以特异性地抵抗由 H2O2 和超氧化物生成剂 menadione 引起的氧化应激。令人惊讶的是，当与硫醇修饰剂结合时，肉碱对生存有不利影响。氧化应激反应的核心元素，特别是转录因子 Yap1p 和 Skn7p，被证明是肉碱保护作用所必需的，但几个下游效应物是可有可无的。基于 DNA 微阵列的分析确定 Cyc3p，一种细胞色素 c 血红素裂解酶，是肉碱在氧化应激过程中的重要作用。这些发现建立了与肉碱相关表型的直接遗传联系，该表型独立于穿梭系统，并表明酿酒酵母应该为进一步阐明肉碱的生理作用提供一个有用的模型。
