Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1...Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1), a plastid-localized enoyl-ACP reductase essential for de novo fatty acid biosynthesis in Arabidopsis thaliana, leads to the increased malate export from chloroplasts to mitochondria, and the subsequent accumulation of mitochondria-generated ROS and PCD. In this study, we report the identification and characterization of a mod1 suppressor, som592. SOM592 encodes mitochondrion-localized NAD^+ transporter 2(NDT2). We show that the mitochondrial NAD pool is elevated in the mod1 mutant. The som592 mutation fully suppressed mitochondrial NADH hyper-accumulation, ROS production, and PCD in the mod1 mutant, indicating a causal relationship between mitochondrial NAD accumulation and ROS/PCD phenotypes. We also show that in wild-type plants, the mitochondrial NAD+uptake is involved in the regulation of ROS production in response to continuous photoperiod. Elevation of the alternative respiration pathway can suppress ROS accumulation and PCD in mod1, but leads to growth restriction. These findings uncover a regulatory mechanism for mitochondrial ROS production via NADH homeostasis in Arabidopsis thaliana that is likely important for growth regulation in response to altered photoperiod.展开更多
Immune-mediated activation of tryptophan（TRYP） catabolism via the kynurenine pathway（KP） is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic p...Immune-mediated activation of tryptophan（TRYP） catabolism via the kynurenine pathway（KP） is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites,including quinolinic acid（QUIN） in neuroinflammatory neurological disorders,including Alzheimer＇s disease（AD）,multiple sclerosis,amylotropic lateral sclerosis（ALS）,and AIDS related dementia complex（ADC）.Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response.Under physiological conditions,QUIN is metabolized to the essential pyridine nucleotide,nicotinamide adenine dinucleotide（NAD＋）,which represents an important metabolic cofactor and electron transporter.NAD＋ also serves as a substrate for the DNA ‘nick sensor＇ and putative nuclear repair enzyme,poly（ADP-ribose） polymerase（PARP）.Free radical initiated DNA damage,PARP activation and NAD＋ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.展开更多
Three new nicotinamide adenine dinucleotide(NAD) analogs were synthesized,and their characteristics as cofactors for Escherichia coli malic enzyme(ME) and its double mutant ME L310R/Q401C were analyzed.Each pair of th...Three new nicotinamide adenine dinucleotide(NAD) analogs were synthesized,and their characteristics as cofactors for Escherichia coli malic enzyme(ME) and its double mutant ME L310R/Q401C were analyzed.Each pair of the NAD analog and the double mutant showed good orthogonality to the natural pair of NAD and ME in terms of catalyzing oxidative decarboxylation of L-malic acid.Results indicated that molecular interactions between redox enzyme and cofactor could be further explored to generate new bioorthogonal redox systems.展开更多
Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings incre...Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings increased during the past centuries. Recent research established vital roles for NAD＋ and its precursors in protecting and maintaining the redox homeostasis in cells, which might be applicable therapeutically to prevent cell degeneration. Notably, the contribution of NAD＋ metabolites to lifespan extension in model systems indicates that the potential beneficial effects of NAD＋ precursors. In this mini review, by introducing the background of NAD＋-consuming enzymes in ＂caloric restriction＂, we focus on NAD＋ and its precursors in diet, with further emphasis on its association with health and diseases. We also provide insights in future utilization ofNAD＋ and its precursors as nutrition supplement for lifespan extension.展开更多
基金supported by the National Natural Science Foundation of China (31521001, 91854103, 31661143025)
文摘Reactive oxygen species(ROS) play a crucial role in numerous biological processes in plants, including development, responses to environmental stimuli, and programmed cell death(PCD). Deficiency in MOSAIC DEATH 1(MOD1), a plastid-localized enoyl-ACP reductase essential for de novo fatty acid biosynthesis in Arabidopsis thaliana, leads to the increased malate export from chloroplasts to mitochondria, and the subsequent accumulation of mitochondria-generated ROS and PCD. In this study, we report the identification and characterization of a mod1 suppressor, som592. SOM592 encodes mitochondrion-localized NAD^+ transporter 2(NDT2). We show that the mitochondrial NAD pool is elevated in the mod1 mutant. The som592 mutation fully suppressed mitochondrial NADH hyper-accumulation, ROS production, and PCD in the mod1 mutant, indicating a causal relationship between mitochondrial NAD accumulation and ROS/PCD phenotypes. We also show that in wild-type plants, the mitochondrial NAD+uptake is involved in the regulation of ROS production in response to continuous photoperiod. Elevation of the alternative respiration pathway can suppress ROS accumulation and PCD in mod1, but leads to growth restriction. These findings uncover a regulatory mechanism for mitochondrial ROS production via NADH homeostasis in Arabidopsis thaliana that is likely important for growth regulation in response to altered photoperiod.
基金NHMRC Postdoctoral Fellowship at the University of New South Wales
文摘Immune-mediated activation of tryptophan（TRYP） catabolism via the kynurenine pathway（KP） is a consistent finding in all inflammatory disorders.Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites,including quinolinic acid（QUIN） in neuroinflammatory neurological disorders,including Alzheimer＇s disease（AD）,multiple sclerosis,amylotropic lateral sclerosis（ALS）,and AIDS related dementia complex（ADC）.Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response.Under physiological conditions,QUIN is metabolized to the essential pyridine nucleotide,nicotinamide adenine dinucleotide（NAD＋）,which represents an important metabolic cofactor and electron transporter.NAD＋ also serves as a substrate for the DNA ‘nick sensor＇ and putative nuclear repair enzyme,poly（ADP-ribose） polymerase（PARP）.Free radical initiated DNA damage,PARP activation and NAD＋ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease.
基金supported by the National Basic Research Program of China (2012CB721103)the National Natural Science Foundation of China (21102143)
文摘Three new nicotinamide adenine dinucleotide(NAD) analogs were synthesized,and their characteristics as cofactors for Escherichia coli malic enzyme(ME) and its double mutant ME L310R/Q401C were analyzed.Each pair of the NAD analog and the double mutant showed good orthogonality to the natural pair of NAD and ME in terms of catalyzing oxidative decarboxylation of L-malic acid.Results indicated that molecular interactions between redox enzyme and cofactor could be further explored to generate new bioorthogonal redox systems.
基金We gratefully acknowledge the National Natural Science Foundation of China （No. 21502026）, Shenzhen Science and Technology Innovation Committee （JCYJ20140411112047887） for their support to Yanchao Pan. We thank Dr. Zhen Xie for comments on the manuscript.
文摘Aging is a complex issue due to its nature in progressive physiological and functional decay. As better medicine, technology, and living conditions became accessible to many people, the longevity of human beings increased during the past centuries. Recent research established vital roles for NAD＋ and its precursors in protecting and maintaining the redox homeostasis in cells, which might be applicable therapeutically to prevent cell degeneration. Notably, the contribution of NAD＋ metabolites to lifespan extension in model systems indicates that the potential beneficial effects of NAD＋ precursors. In this mini review, by introducing the background of NAD＋-consuming enzymes in ＂caloric restriction＂, we focus on NAD＋ and its precursors in diet, with further emphasis on its association with health and diseases. We also provide insights in future utilization ofNAD＋ and its precursors as nutrition supplement for lifespan extension.
