Using genetically encoded heme sensors to probe the mechanisms of heme uptake and homeostasis in Candida albicans.
Using genetically encoded heme sensors to probe the mechanisms of heme uptake and homeostasis in Candida albicans.
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使用基因编码的血红素传感器来探究白色念珠菌的血红素摄取和稳态机制。
DOI：
10.1111/cmi.13282
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发表时间：
2021-03
影响因子：
3.4
通讯作者：
Kornitzer D
中科院分区：
文献类型：
--
作者：
Weissman Z;Pinsky M;Donegan RK;Reddi AR;Kornitzer D
白色念珠菌是一种主要的真菌病原体，可以利用氯化血红素和血红蛋白作为铁源，在缺铁的宿主环境。而C.白色念珠菌是血红素原养型，我们在这里表明，它也可以有效地利用外部血红素作为细胞血红素源。使用遗传编码的比率荧光血红素传感器，我们表明，血红素提取血红蛋白和游离血红素进入细胞具有不同的动力学。作为血红蛋白提供的血红素通过CFEM（常见于真菌细胞外膜）血细胞级联被吸收，并在几个小时内到达细胞质，而通过CFEM依赖性和独立途径进入游离氯化血红素要快得多，不到一个小时。为了防止细胞外血红素的流入达到细胞质中的毒性水平，细胞部署血红素加氧酶Hmx1。Hmx1以前被认为是参与利用血红蛋白和氯化血红素作为铁源，但我们发现，它主要是为了防止血红素毒性。两者合计，新的血红素传感器与遗传分析相结合，揭示了血红素进口和稳态的真菌机制的新细节，这是平衡血红素作为必要的辅因子和潜在的铁源对抗其毒性所必需的。
Candida albicans is a major fungal pathogen that can utilize hemin and hemoglobin as iron sources in the iron-scarce host environment. While C. albicans is a heme prototroph, we show here that it can also efficiently utilize external heme as a cellular heme source. Using genetically encoded ratiometric fluorescent heme sensors, we show that heme extracted from hemoglobin and free hemin enter the cells with different kinetics. Heme supplied as hemoglobin is taken up via the CFEM (Common in Fungal Extracellular Membrane) hemophore cascade, and reaches the cytoplasm over several hours, whereas entry of free hemin via CFEM-dependent and independent pathways is much faster, less than an hour. To prevent an influx of extracellular heme from reaching toxic levels in the cytoplasm, the cells deploy Hmx1, a heme oxygenase. Hmx1 was previously suggested to be involved in utilization of hemoglobin and hemin as iron sources, but we find that it is primarily required to prevent heme toxicity. Taken together, the combination of novel heme sensors with genetic analysis revealed new details of the fungal mechanisms of heme import and homeostasis, necessary to balance the uses of heme as essential cofactor and potential iron source against its toxicity.
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影响因子：
30.3
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
通讯作者：
Noble SM
影响因子：
5.7
作者：
Caza M;Kronstad JW
通讯作者：
Kronstad JW
DOI：
10.3390/jof3040057
发表时间：
2017-10-18
期刊：
Journal of fungi (Basel, Switzerland)
影响因子：
--
作者：
Bongomin F;Gago S;Oladele RO;Denning DW
通讯作者：
Denning DW
DOI：
10.1534/g3.117.300224
发表时间：
2017-11-06
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Azadmanesh J;Gowen AM;Creger PE;Schafer ND;Blankenship JR
通讯作者：
Blankenship JR
影响因子：
4.8
作者：
MAINES, MD
通讯作者：
MAINES, MD