PDF(Pubmed)
Abstract：
Heme is an essential cofactor for multiple cellular processes in most organisms. In developing erythroid cells, the demand for heme synthesis is high, but is significantly lower in non-erythroid cells. While the biosynthesis of heme in metazoans is well understood, the tissue-specific regulation of the pathway is less explored. To better understand this, we analyzed the mitochondrial heme metabolon in erythroid and non-erythroid cell lines from the perspective of ferrochelatase (FECH), the terminal enzyme in the heme biosynthetic pathway. Affinity purification of FLAG-tagged-FECH, together with mass spectrometric analysis, was carried out to identify putative protein partners in human and murine cell lines. Proteins involved in the heme biosynthetic process and mitochondrial organization were identified as the core components of the FECH interactome. Interestingly, in non-erythroid cell lines, the FECH interactome is highly enriched with proteins associated with the tricarboxylic acid (TCA) cycle. Overall, our study shows that the mitochondrial heme metabolon in erythroid and non-erythroid cells has similarities and differences, and suggests new roles for the mitochondrial heme metabolon and heme in regulating metabolic flux and key cellular processes.
摘要：
血红素是大多数生物体中多个细胞过程的必需辅因子。在发育中的红系细胞中，对血红素合成的需求很高，但在非红系细胞中明显更低。虽然血红素在后生动物中的生物合成是众所周知的，该途径的组织特异性调控研究较少。为了更好地理解这一点，我们从铁螯合酶（FECH）的角度分析了红系和非红系细胞系中的线粒体血红素代谢产物，血红素生物合成途径的末端酶。FLAG标记的FECH的亲和纯化，连同质谱分析，进行了鉴定人和鼠细胞系中推定的蛋白质伴侣。参与血红素生物合成过程和线粒体组织的蛋白质被鉴定为FECH相互作用组的核心成分。有趣的是,在非红系细胞系中，FECH相互作用组富含与三羧酸（TCA）循环相关的蛋白质。总的来说,我们的研究表明，红细胞和非红系细胞中的线粒体血红素代谢产物具有相似性和差异性，并提示线粒体血红素代谢物和血红素在调节代谢通量和关键细胞过程中的新作用。
