Mesquita Inês, Vergnes Baptiste, Silvestre Ricardo
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Exp Suppl. 2018;109:197-220. doi: 10.1007/978-3-319-74932-7_4.
The cofactors nicotinamide adenine dinucleotide (NAD) and its phosphate form, NADP, are crucial molecules present in all living cells. The delicate balance between the oxidized and reduced forms of these molecules is tightly regulated by intracellular metabolism assuring the maintenance of homeostatic conditions, which are essential for cell survival and proliferation. A recent cluster of data has highlighted the importance of the intracellular NAD/NADH and NADP/NADPH ratios during host-pathogen interactions, as fluctuations in the levels of these cofactors and in precursors' bioavailability may condition host response and, therefore, pathogen persistence or elimination. Furthermore, an increasing interest has been given towards how pathogens are capable of hijacking host cell proteins in their own advantage and, consequently, alter cellular redox states and immune function. Here, we review the basic principles behind biosynthesis and subcellular compartmentalization of NAD and NADP, as well as the importance of these cofactors during infection, with a special emphasis on pathogen-driven modulation of host NAD/NADP levels and contribution to the associated immune response.
辅因子烟酰胺腺嘌呤二核苷酸(NAD)及其磷酸化形式NADP是所有活细胞中存在的关键分子。这些分子氧化态和还原态之间的微妙平衡受到细胞内代谢的严格调控,以确保维持内稳态条件,这对细胞存活和增殖至关重要。最近一系列数据突出了宿主-病原体相互作用期间细胞内NAD/NADH和NADP/NADPH比值的重要性,因为这些辅因子水平及其前体生物利用度的波动可能影响宿主反应,进而影响病原体的持续存在或清除。此外,人们越来越关注病原体如何能够利用宿主细胞蛋白为自身谋利,从而改变细胞氧化还原状态和免疫功能。在此,我们综述NAD和NADP生物合成及亚细胞区室化背后的基本原理,以及这些辅因子在感染期间的重要性,特别强调病原体驱动的宿主NAD/NADP水平调节及其对相关免疫反应的贡献。