Absence of MMF1 disrupts heme biosynthesis by targeting Hem1pin Saccharomyces cerevisiae,Yeast

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Absence of MMF1 disrupts heme biosynthesis by targeting Hem1pin Saccharomyces cerevisiae
Yeast ( IF 2.2 ) Pub Date : 2021-09-24 , DOI: 10.1002/yea.3670
Gregory H Whitaker ₁ , Dustin C Ernst ₂ , Diana M Downs ₁

Affiliation

The RidA subfamily of the Rid (YjgF/YER057c/UK114) superfamily of proteins is broadly distributed and found in all domains of life. RidA proteins are enamine/imine deaminases. In the organisms that have been investigated, lack of RidA results in accumulation of the reactive enamine species 2-aminoacrylate (2AA) and/or its derivative imine 2-iminopropanoate (2IP). The accumulated enamine/imine species can damage specific pyridoxal phosphate (PLP)-dependent target enzymes. The metabolic imbalance resulting from the damaged enzymes is organism specific and based on metabolic network configuration. Saccharomyces cerevisiae encodes two RidA homologs, one localized to the cytosol and one to the mitochondria. The mitochondrial RidA homolog, Mmf1p, prevents enamine/imine stress and is important for normal growth and maintenance of mitochondrial DNA. Here, we show that Mmf1p is necessary for optimal heme biosynthesis. Biochemical and/or genetic data herein support a model in which accumulation of 2AA and or 2IP, in the absence of Mmf1p, inactivates Hem1p, a mitochondrially located PLP-dependent enzyme required for heme biosynthesis.

中文翻译：

MMF1 的缺失会通过靶向酿酒酵母 Hem1pin 来破坏血红素生物合成

Rid (YjgF/YER057c/UK114) 蛋白质超家族的 RidA 亚家族分布广泛，存在于生命的各个领域。 RidA 蛋白是烯胺/亚胺脱氨酶。在已研究的生物体中，缺乏 RidA 会导致反应性烯胺物质 2-氨基丙烯酸酯 (2AA) 和/或其衍生物亚胺 2-亚氨基丙酸酯 (2IP) 的积累。积累的烯胺/亚胺物质会损害特定的磷酸吡哆醛 (PLP) 依赖性靶酶。由受损酶引起的代谢失衡是生物体特异性的并且基于代谢网络配置。酿酒酵母编码两种 RidA 同源物，一种定位于细胞质，一种定位于线粒体。线粒体 RidA 同源物 Mmf1p 可防止烯胺/亚胺应激，对于线粒体 DNA 的正常生长和维护非常重要。在这里，我们证明 Mmf1p 对于最佳血红素生物合成是必需的。本文的生化和/或遗传数据支持这样的模型：在不存在 Mmf1p 的情况下，2AA 和/或 2IP 的积累会使 Hem1p 失活，Hem1p 是血红素生物合成所需的位于线粒体的 PLP 依赖性酶。

更新日期：2021-09-24

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