血红素是参与重要生理过程的蛋白质的辅基。它参与,例如,在氧化还原反应中,由于其中心铁原子的氧化态可变,对细胞代谢至关重要。然而,过量的血红素可以是细胞毒性由于其促氧化特性。因此,细胞内血红素水平的控制确保了生物体的生存,尤其是那些一生中处理高浓度血红素的人,例如吸血昆虫。最初归因于猫白血病病毒C受体(FLVCR)的血红素的出口最近受到质疑,在哺乳动物中发现相同受体吸收胆碱后。这里,我们发现RpFLVCR是食血昆虫罗氏中肠的血红素出口国,查加斯病的病媒.沉默RpFLVCR降低了血淋巴血红素水平,并增加了细胞内双半胱氨酸-胆绿素的水平,表明血红素保留在中肠细胞内。FLVCR沉默导致血红素加氧酶(HO)表达增加,铁蛋白,和丝裂铁蛋白mRNA,同时下调铁进口商Malvolio1和2。相比之下,HO基因沉默增加了FLVCR和Malvolio的表达并下调了铁蛋白,揭示血红素降解/出口和铁运输/储存途径之间的串扰。此外,RpFLVCR沉默强烈增加了氧化剂的产生和脂质过氧化,细胞色素C氧化酶活性降低,和激活的线粒体生物发生,在RpHO沉默的昆虫中未观察到的影响。这些数据支持FLVCR作为血红素出口商的功能,在血红素/铁代谢和维持氧化还原平衡中起关键作用,特别是在适应于面对极高血红素浓度的生物体中。
Heme is a prosthetic group of proteins involved in vital physiological processes. It participates, for example, in redox reactions crucial for cell metabolism due to the variable oxidation state of its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The export of heme initially attributed to the feline leukemia virus C receptor (FLVCR) has recently been called into question, following the discovery of choline uptake by the same receptor in mammals. Here, we found that RpFLVCR is a heme exporter in the midgut of the hematophagous insect
Rhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl-biliverdin, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity, and activated mitochondrial biogenesis, effects not observed in RpHO-silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.