?Labile? heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae
?Labile? heme critically regulates mitochondrial biogenesis through the transcriptional co-activator Hap4p in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.ra120.012739
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发表时间：
2020-04-10
影响因子：
4.8
通讯作者：
Devin, Anne
中科院分区：
文献类型：
--
作者：
Bouchez, Cyrielle L.;Yoboue, Edgar D.;Devin, Anne
血红素（铁原卟啉IX）是参与代谢途径（例如通过线粒体呼吸链的氧运输和电子转移）的酶的众所周知的辅基。然而，血红素也被证明是一个重要的调节分子（如？不稳定？血红素）用于哺乳动物、酵母和细菌中的多种过程，如翻译、激酶活性和转录。利用酵母菌株缺乏血红素生产，使控制调制和监测不稳定的血红素水平，在这里，我们研究了不稳定的血红素在线粒体生物合成的调节中的作用。这一过程由酵母中的HAP复合物调节。使用几个生化检测沿着EM和荧光显微镜，尽我们所知，我们第一次表明，细胞不稳定血红素是至关重要的翻译后调节HAP复合物的活性，最有可能通过稳定的转录共激活因子Hap4p。因此，我们发现，不稳定血红素调节线粒体生物合成和细胞生长。我们的研究结果强调了细胞代谢产物调节线粒体生物合成的新机制。
Heme (iron protoporphyrin IX) is a well-known prosthetic group for enzymes involved in metabolic pathways such as oxygen transport and electron transfer through the mitochondrial respiratory chain. However, heme has also been shown to be an important regulatory molecule (as ?labile? heme) for diverse processes such as translation, kinase activity, and transcription in mammals, yeast, and bacteria. Taking advantage of a yeast strain deficient for heme production that enabled controlled modulation and monitoring of labile heme levels, here we investigated the role of labile heme in the regulation of mitochondrial biogenesis. This process is regulated by the HAP complex in yeast. Using several biochemical assays along with EM and epifluorescence microscopy, to the best of our knowledge, we show for the first time that cellular labile heme is critical for the post-translational regulation of HAP complex activity, most likely through the stability of the transcriptional co-activator Hap4p. Consequently, we found that labile heme regulates mitochondrial biogenesis and cell growth. The findings of our work highlight a new mechanism in the regulation of mitochondrial biogenesis by cellular metabolites.