The heme synthesis-export system regulates the tricarboxylic acid cycle flux and oxidative phosphorylation
The heme synthesis-export system regulates the tricarboxylic acid cycle flux and oxidative phosphorylation
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DOI：
10.1016/j.celrep.2021.109252
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发表时间：
2021-06-15
期刊：
影响因子：
8.8
通讯作者：
Tolosano, Emanuela
中科院分区：
文献类型：
--
作者：
Fiorito, Veronica;Allocco, Anna Lucia;Tolosano, Emanuela
血红素是一种对细胞能量代谢至关重要的含铁卟啉。在增殖细胞中通常观察到高速率的血红素合成。此外，细胞表面血红素输出体猫白血病病毒C亚群受体1a（FLVCR 1a）在几种肿瘤类型中过表达。然而，血红素合成和输出在高度增殖的细胞中增强的原因仍然未知。在这里，我们说明了血红素合成和血红素出口之间的功能轴：血红素流出通过质膜维持血红素合成，和实施的两个过程下调三羧酸（TCA）循环通量和氧化磷酸化。相反，血红素输出的抑制减少血红素合成，并促进TCA循环燃料和流量以及氧化磷酸化。这些数据表明血红素合成-输出系统调节TCA循环和氧化代谢，并为观察到这两个过程在高能量需求的细胞中增强提供了机制基础。
Heme is an iron-containing porphyrin of vital importance for cell energetic metabolism. High rates of heme synthesis are commonly observed in proliferating cells. Moreover, the cell-surface heme exporter feline leukemia virus subgroup C receptor 1a (FLVCR1a) is overexpressed in several tumor types. However, the reasons why heme synthesis and export are enhanced in highly proliferating cells remain unknown. Here, we illustrate a functional axis between heme synthesis and heme export: heme efflux through the plasma membrane sustains heme synthesis, and implementation of the two processes down-modulates the tricarboxylic acid (TCA) cycle flux and oxidative phosphorylation. Conversely, inhibition of heme export reduces heme synthesis and promotes the TCA cycle fueling and flux as well as oxidative phosphorylation. These data indicate that the heme synthesis-export system modulates the TCA cycle and oxidative metabolism and provide amechanistic basis for the observation that both processes are enhanced in cells with high-energy demand.