NAD

Figures & data

Figure 1. Metabolism of nicotinamide adenine dinucleotide (NAD) in plants and its responses to stress. De novo biosynthesis, recycling, catabolism and utilization of the NAD⁺ molecule. Plain arrows indicate experimentally demonstrated reactions. Dashed arrows refer to condensed biochemical steps or experimentally non-demonstrated reactions. ADP: adenine diphosphate; AMP: adenine monophosphate; AO: aspartate oxidase; ATP: adenine triphosphate; cADPR(P): cyclic ADP-ribose (phospshate); ReT and PeT: respiratory and photosynthetic electron transport chains, respectively; NaAD: nicotinic acid adenine dinucleotide; NADK: NAD kinase; NADP: NAD phosphate; NADP pase: NADP phosphatase; NaMN: nicotinic acid mononucleotide; NaMNAT: NaMN adenylyltransferase; NADS: NAD synthetase; NaPT: nicotinate phosphoribosyltransferase; NDT: NAD⁺ carrier; NIC: nicotinamidase; PARP: poly-ADP-ribose polymerase; PXN: peroxisomal NAD carrier; QPT: quinolinate phosphoribosyltransferase; QS: quinolinate synthase; ROS: reactive oxygen species; TCAP: tricarboxylic acid pathway.

Table 1. Mutants and engineered plants used to illustrate the role of NAD in plant immunity

Plant line	Species	Genotype	Impact on NAD or its derivative	Pathogen responses	References
CD38 OE	Human enzyme in Arabidopsis	OE	Expressing the human NAD(P)-metabolizing ectoenzyme	altered activation of SAR	[68]
CMSII	Nicotiana	in vitro wild-type protoplast culture	absence of respiratory complex I associated with higher NAD(H)	increased resistance to oxidative stress and a viral pathogen	[56,57]
fin4	Arabidopsis	T-DNA	impaired NAD biosynthesis	affected in several responses to pathogen attacks: PAMP-triggered ROS burst evolved by NADPH oxidases RBOHD and pathogen-related stomatal closure	[71]
gfg1	Arabidopsis	T-DNA	encoded a NUDX increased NADH/NAD^+ ratio	increased ROS and NADH improved resistance to bacterial pathogens	[88]
nadC OE	E.coli gene in Arabidopsis	OE	inducible increase in intracellular NAD/P(H) content in leaves	enhanced resistance to avirulent Pst-AvrRpm1 associated with SA accumulation and altered redox dynamics	[18]
NADK2 OE	Arabidopsis gene in Rice	OE	build-up of the NADP(H) pool	enhanced tolerance to oxidative damage	[58]
nudt7	Arabidopsis	T-DNA	increased NADH/NAD ratio	activation of pathways dependent and independent of NPR1 and SA regulation of an EDS1- and PAD4-dependent but SA-independent signaling pathway in plant defense responses	[82,84,86]
parg1, parg2	Arabidopsis	T-DNA	incapable of removing ADPr from poly-ADPr chains	accelerated onset of disease symptoms upon fungal infection	[84,103]
parp1, parp2	Arabidopsis	T-DNA	accumulated poly-ADPr chains	increased resistance to stresses (reducing NAD^+ breakdown and consequently energy consumption)	[49,100]
PARP1, PARP2 OE	Arabidopsis	OE	ADPr removed from poly-ADPr chains	reduced incidence of H2O2-induced DNA nicks	[49,99,100,101]
rbohD and F	Arabidopsis	Transposon insertion	impaired NADPH oxidase function in response to stress	extracellular NAD-defense responses (independent of NADPH oxidases encoded by AtrbohD and AtrbohF) the reducing power carried by NADPH could not influence PR genes expression.	[19]
SAG OE	Arabidopsis	OE	redox-related protein	responses to biotic stress via interaction with proteins that participate in mitochondrial ROS signaling.	[67]
srt2	Arabidopsis	T-DNA	impaired function of NAD-dependent histone deacetylation causing altered DNA repair, cell cycle, death and aging	improved resistance to Pst DC3000 associated with the induction of PR1 overexpression of SA biosynthesis-related genes (PAD4, EDS5 and SID2)	[113]
SRT2 OE	Arabidopsis	OE	altered function of NAD-dependent histone deacetylation leading to altered DNA repair, cell cycle, death and aging	bacterial hyper-susceptibility and impaired PR1 induction downregulation of PAD4, EDS5 and SID2	[107]

Figure 2. NAD, a key component of the plant immunity signaling network: a model. Manipulation of NAD biosynthesis (AO, QPT) or utilization (PARP; PARG; NUDIX hydrolases; SIRTUINS) alters redox balance of pyridine nucleotides (PNs) which interferes with plant defense responses. Modified pools of PNs induce calcium binding protein genes (CaBP)¹⁸ and activate Ca²⁺ influx that stimulates NADPH oxidase (RBOH) activity therefore increasing ROS generation. Oxidative burst is believed to favor the signal amplification loop involving salicylic acid (SA).^2,115 PNs also cause induction of SA-biosynthetic gene isochorismate synthase (ICS1) and lead to SA accumulation.¹⁸ SA can activate pathogen-related (PR) genes by pathways that are dependent and independent of the non-repressor of PR1 (NPR1) component.¹⁷ It remains unclear how Ca²⁺ triggers SA-dependent resistance. While it is not totally understood how PNs activate RBOH, the perturbation in NAD/P(H) pools disturbs redox signaling by inducing redox-related genes (glutathione S-transferase: GST; perodixase; PRX; senescence associated gene: SAG). Glutathione (GSH) which is regenerated by the reducing power of NADPH is also potentially altered by modified PNs levels. Another redox-related response upon high NAD content relies on the alteration of the methionine (Met) pools and the induction of Met sulfoxide reductase genes (MSR) that are involved in reducing Met sulfoxide residues (MetSO) back to Met.¹⁸ Dashed arrows refer to possible signaling connections.

Pétriacq P, de Bont L, Hager J, Didierlaurent L, Mauve C, Guérard F, et al. Inducible NAD overproduction in Arabidopsis alters metabolic pools and gene expression correlated with increased salicylate content and resistance to Pst-AvrRpm1. Plant J 2012; 70:650 - 65; http://dx.doi.org/10.1111/j.1365-313X.2012.04920.x; PMID: 22268572

 PubMed Web of Science ®Google Scholar

Torres MA. ROS in biotic interactions. Physiol Plant 2010; 138:414 - 29; http://dx.doi.org/10.1111/j.1399-3054.2009.01326.x; PMID: 20002601

 PubMed Web of Science ®Google Scholar

Torres MA, Jones JDG, Dangl JL. Reactive oxygen species signaling in response to pathogens. Plant Physiol 2006; 141:373 - 8; http://dx.doi.org/10.1104/pp.106.079467; PMID: 16760490

 PubMed Web of Science ®Google Scholar

Zhang X, Mou Z. Extracellular pyridine nucleotides induce PR gene expression and disease resistance in Arabidopsis. Plant J 2009; 57:302 - 12; http://dx.doi.org/10.1111/j.1365-3-13X.2008.03687.x; PMID: 18798871

 PubMed Web of Science ®Google Scholar