Post-print of: Plant Signaling & Behavior 8:5, e24007; May 2013
http://dx.doi.org/10.4161/psb.24007
L-Cysteine Desulfhydrase 1 modulates the generation of the signaling
molecule sulfide in plant cytosol
Luis C. Romero, Irene García, Cecilia Gotor*
Instituto de Bioquímica Vegetal y Fotosíntesis; Consejo Superior de Investigaciones Científicas
and Universidad de Sevilla; Sevilla, Spain
Keywords: Arabidopsis, autophagy, cysteine, cytosolic sulfide, transcriptional profile
*Correspondence to: Cecilia Gotor; E-mail: gotor@ibvf.csic.es
Addendum to: Álvarez C, et al. Plant Cell 2012; 24:4621-4634; PMID: 23144183;
http://dx.doi.org/10.1105/tpc.112.105403.
1
ABSTRACT
Consistent with data in animal systems, experimental evidence highlights sulfide as a signaling
molecule of equal importance to NO and H2O2 in plant systems. In mammals, two cytosolic
enzymes, cystathionine -synthase (CBS) and cystathionine -lyase (CSE), have been shown to
be responsible for the endogenous production of sulfide. L-cysteine desulfhydrase 1 (DES1) has
been recently established as the only enzyme that is involved in the generation of hydrogen
sulfide in plant cytosol. Although plants have an available source of sulfide within chloroplasts,
the basic stromal pH prevents sulfide release into the cytosol. Therefore, DES1 is essential for
the production of sulfide for signaling purposes.
2
For a long time, sulfide has been known primarily as a toxic molecule that is hazardous to the
environment. Recently, however, sulfide has been recognized as a gasotransmitter (gaseous
molecule that transmits information between cells) of equal importance to CO or NO in animal
systems. Numerous reports describing the biological effects of sulfide highlight its physiological
importance, and there is no doubt that most cells in mammals are able to produce and metabolize
sulfide in a precise, regulated manner 1. However, identifying the molecular targets of sulfide
and deciphering its mechanism of action remain challenging. A small number of direct targets,
including ion channels, glyceraldehyde phosphate dehydrogenase (GAPDH), actin, tubulin,
complex IV of the mitochondrial electron transport chain, and tyrosine phosphatase PTP1B, have
been identified so far. In these cases, sulfhydration of reactive cysteines has been observed 2.
Therefore, the sulfhydration can be considered a physiologic posttranslational modification for
proteins, and previous studies have indicated that this modification can be regulated by
competition between the nitrosylation and sulfhydration of the same cysteine residues. This
competition has been observed on GAPDH protein 3.
In recent years, experimental evidence emerging from numerous plant biology studies has
shown H2S to be a signaling molecule of equal importance to NO and H2O2. Sulfide has been
shown to be involved in protection against copper, aluminum and boron stress
4-7
, in the
improvement of drought resistance, and in the promotion of heat and salinity tolerance
8-10
.
Furthermore, sulfide has been suggested to play a role in regulating photosynthesis and flower
senescence and in prolonging the postharvest shelf life of fruits 11-13. This molecule has also been
identified as a component of the ABA signaling pathway in guard cells 14,15.
Our recent research has demonstrated that sulfide per se, but not sulfide as sulfur nutrient,
exerts a general effect on autophagy through negative regulation
16
. Thus, it seems that
independently of the sulfur nutrition status of the plant, in this case Arabidopsis thaliana, sulfide
that is specifically generated inside the cytosol and that results from the degradation of cysteine
3
acts as a signaling molecule and regulates the process of autophagy
17
. Another interesting
observation that warrants further investigation is that sulfide seems to behave as a modulator of
the transcriptional profile of the plant at its mature developmental stage. This hypothesis was
proposed because when the capacity of the cytosol to release sulfide is reduced, the plant
transcriptome is dramatically altered. This situation can be reversed by restoring the plant’s
capacity to generate sulfide (GSE32566).
It has recently been established that the main sources of endogenous production of H2S in
mammals are the enzymatic reactions catalyzed by cystathionine -synthase (CBS) and
cystathionine -lyase (CSE)
1,18
. Both enzymes are known for their participation in the
transsulfuration pathway, which is critical for the synthesis of cysteine from methionine (the
latter being the source of sulfur from diet in animals). The two enzymes have also been
demonstrated to be the main proteins that are responsible for generating hydrogen sulfide from
cysteine (Fig. 1). Both CBS and CSE use pyridoxal 5’-phosphate (PLP) as a cofactor and are
exclusively located in the cytosol. We recently identified an analogous PLP-dependent enzyme
with L-cysteine desulfhydrase activity, DES1, located in the cytosol in Arabidopsis thaliana
plants 16,19. DES1 is the only enzyme unequivocally established to be involved in the degradation
of cysteine and the concomitant generation of hydrogen sulfide in the cytosol (Fig. 1). We have
reached the conclusion that DES1 in the plant cell could be responsible for modulating the
generation of sulfide for signaling in important processes, such as the progression of autophagy
17
. Doubt regarding this role could arise from the fact that in plants, the chloroplast is the main
source of sulfide, which results from sulfate reduction in the sulfur assimilation pathway 20. This
chloroplastic sulfide is thought to overflow into the cytosol. However, hydrogen sulfide is
weakly acidic and dissociates in aqueous solution into H+ and SH-. This ionized form cannot
permeate membranes
21
. Thus, at the pH of 8.5 maintained by the chloroplast stroma under
illumination, sulfide is mainly present in its charged form and is therefore unable to transport
4
across the chloroplast envelope.
In conclusion, we suggest that DES1 modulates the production of sulfide in the plant cytosol
and that this sulfide is utilized by the plant for signaling purposes. This hypothesis yields many
areas of potential investigation, such as the mechanism underlying this modulation, the specific
function of DES1 in the signaling and control of different plant processes, the subcellular/tissue
localization and regulation of the enzyme, and the mode of action for and specific targets of the
DES1-generated sulfide. Our present investigation is committed to answering some of these
important questions.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We would like to thank the European Regional Development Fund, the Ministerio de Economía
y Competitividad of Spain (grant no. BIO2010-15201 and CSD2007–00057) and Junta de
Andalucía of Spain (grant no. CVI-7190) for their financial support.
5
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Legend to Figure
Figure 1. Enzymatic generation of sulfide from cysteine. Cystathionine -synthase (CBS) and
cystathionine -lyase (CSE) catalyze this process in mammals; in plants, L-cysteine
desulfhydrase 1 (DES1) performs this function.
9
Figure 1
Cysteine
CBS
DES1
CSE
Sulfide
10