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Glutathione transferase (GST) is a superfamily of ubiquitous enzymes, multigenic in numerous organisms and which generally present homodimeric structures. GSTs are involved in numerous biological functions such as chemical detoxification as well as chemoperception in mammals and insects. GSTs catalyze the conjugation of their cofactor, reduced glutathione (GSH), to xenobiotic electrophilic centers. To achieve this catalytic function, GSTs are comprised of a ligand binding site and a GSH binding site per subunit, which is very specific and highly conserved; the hydrophobic substrate binding site enables the binding of diverse substrates. In this work, we focus our interest in a model organism, the fruit fly Drosophila melanogaster (D. mel), which comprises 42 GST sequences distributed in six classes and composing its GSTome. The goal of this study is to describe the complete structural GSTome of D. mel to determine how changes in the amino acid sequence modify the structural characteristics of GST, particularly in the GSH binding sites and in the dimerization interface. First, we predicted the 3D atomic structures of each GST using the AlphaFold (AF) program and compared them with X-ray crystallography structures, when they exist. We also characterized and compared their global and local folds. Second, we used multiple sequence alignment coupled with AF-predicted structures to characterize the relationship between the conservation of amino acids in the sequence and their structural features. Finally, we applied normal mode analysis to estimate thermal B-factors of all GST structures of D. mel. Particularly, we extracted flexibility profiles of GST and identify key residues and motifs that are systematically involved in the ligand binding/dimerization processes and thus playing a crucial role in the catalytic function. This methodology will be extended to guide the in silico design of synthetic GST with new/optimal catalytic properties for detoxification applications.
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Drosophila melanogaster , Glutationa Transferase , Animais , Drosophila melanogaster/enzimologia , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Sítios de Ligação , Sequência de Aminoácidos , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Modelos Moleculares , Cristalografia por Raios X , Glutationa/metabolismo , Glutationa/química , Multimerização ProteicaRESUMO
This study presents a comprehensive analysis of the dimerization interfaces of fly GSTs through sequence alignment. Our investigation revealed GSTE1 as a particularly intriguing target, providing valuable insights into the variations within Delta and Epsilon GST interfaces. The X-ray structure of GSTE1 was determined, unveiling remarkable thermal stability and a distinctive dimerization interface. Utilizing circular dichroism, we assessed the thermal stability of GSTE1 and other Drosophila GSTs with resolved X-ray structures. The subsequent examination of GST dimer stability correlated with the dimerization interface supported by findings from X-ray structural analysis and thermal stability measurements. Our discussion extends to the broader context of GST dimer interfaces, offering a generalized perspective on their stability. This research enhances our understanding of the structural and thermodynamic aspects of GST dimerization, contributing valuable insights to the field.
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Glutationa Transferase , Multimerização Proteica , Termodinâmica , Animais , Glutationa Transferase/química , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Cristalografia por Raios X , Drosophila melanogaster/enzimologia , Modelos Moleculares , Sequência de Aminoácidos , Drosophila/enzimologiaRESUMO
ß C-S lyases (ß-CSLs; EC 4.4.1.8) are enzymes catalyzing the dissociation of ß carbon-sulfur bonds of cysteine S-conjugates to produce odorant metabolites with a free thiol group. These enzymes are increasingly studied for their role in flavor generation in a variety of food products, whether these processes occur directly in plants, by microbial ß-CSLs during fermentation, or in the mouth under the action of the oral microbiota. Microbial ß-CSLs react with sulfur aroma precursors present in beverages, vegetables, fruits, or aromatic herbs like hop but also potentially with some precursors formed through Maillard reactions in cooked foods such as meat or coffee. ß-CSLs from microorganisms like yeasts and lactic acid bacteria have been studied for their role in the release of polyfunctional thiols in wine and beer during fermentation. In addition, ß-CSLs from microorganisms of the human oral cavity were shown to metabolize similar precursors and to produce aroma in the mouth with an impact on retro-olfaction. This review summarizes the current knowledge on ß-CSLs involved in flavor generation with a focus on enzymes from microbial species present either in the fermentative processes or in the oral cavity. This paper highlights the importance of this enzyme family in the food continuum, from production to consumption, and offers new perspectives concerning the utilization of ß-CSLs as a flavor enhancer.
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Fermentação , Aromatizantes , Humanos , Aromatizantes/metabolismo , Liases de Carbono-Enxofre/metabolismo , Bactérias/enzimologia , Bactérias/metabolismo , PaladarRESUMO
Glutathione transferases are xenobiotic-metabolizing enzymes with both glutathione-conjugation and ligandin roles. GSTs are present in chemosensory tissues and fluids of the nasal/oral cavities where they protect tissues from exogenous compounds, including food molecules. In the present study, we explored the presence of the omega-class glutathione transferase (GSTO1) in the rat oral cavity. Using immunohistochemistry, GSTO1 expression was found in taste bud cells of the tongue epithelium and buccal cells of the oral epithelium. Buccal and lingual extracts exhibited thiol-transferase activity (4.9 ± 0.1 and 1.8 ± 0.1 µM/s/mg, respectively). A slight reduction from 4.9 ± 0.1 to 4.2 ± 0.1 µM/s/mg (p < 0.05; Student's t test) was observed in the buccal extract with 100 µM GSTO1-IN-1, a specific inhibitor of GSTO1. RnGSTO1 exhibited the usual activities of omega GSTs, i.e., thiol-transferase (catalytic efficiency of 8.9 × 104 M-1·s-1), and phenacyl-glutathione reductase (catalytic efficiency of 8.9 × 105 M-1·s-1) activities, similar to human GSTO1. RnGSTO1 interacts with food phytochemicals, including bitter compounds such as luteolin (Ki = 3.3 ± 1.9 µM). Crystal structure analysis suggests that luteolin most probably binds to RnGSTO1 ligandin site. Our results suggest that GSTO1 could interact with food phytochemicals in the oral cavity.
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Glutationa Transferase , Luteolina , Ratos , Animais , Humanos , Glutationa Transferase/metabolismo , Mucosa Bucal/metabolismo , Compostos de Sulfidrila , Glutationa/metabolismoRESUMO
The mucosal pellicle (MP) is a biological film protecting the oral mucosa. It is composed of bounded salivary proteins and transmembrane mucin MUC1 expressed by oral epithelial cells. Previous research indicates that MUC1 expression enhances the binding of the main salivary protein forming the MP, MUC5B. This study investigated the influence of MUC1 structure on MP formation. A TR146 cell line, which does not express MUC1 natively, was stably transfected with genes coding for three MUC1 isoforms differing in the structure of the two main extracellular domains: the VNTR domain, exhibiting a variable number of tandem repeats, and the SEA domain, maintaining the two bound subunits of MUC1. Semi-quantification of MUC1 using dot blot chemiluminescence showed comparable expression levels in all transfected cell lines. Semi-quantification of MUC5B by immunostaining after incubation with saliva revealed that MUC1 expression significantly increased MUC5B adsorption. Neither the VNTR domain nor the SEA domain was influenced MUC5B anchoring, suggesting the key role of the MUC1 N-terminal domain. AFM-IR nanospectroscopy revealed discernible shifts indicative of changes in the chemical properties at the cell surface due to the expression of the MUC1 isoform. Furthermore, the observed chemical shifts suggest the involvement of hydrophobic effects in the interaction between MUC1 and salivary proteins.
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Aroma is among of the most important criteria that indicate the quality of food and beverage products. Aroma compounds can be found as free molecules or glycosides. Notably, a significant portion of aroma precursors accumulates in numerous food products as nonvolatile and flavorless glycoconjugates, termed glycosidic aroma precursors. When subjected to enzymatic hydrolysis, these seemingly inert, nonvolatile glycosides undergo transformation into fragrant volatiles or volatiles that can generate odor-active compounds during food processing. In this context, microbial ß-glucosidases play a pivotal role in enhancing or compromising the development of flavors during food and beverage processing. ß-glucosidases derived from bacteria and yeast can be utilized to modulate the concentration of particular aroma and taste compounds, such as bitterness, which can be decreased through hydrolysis by glycosidases. Furthermore, oral microbiota can influence flavor perception by releasing volatile compounds that can enhance or alter the perception of food products. In this review, considering the glycosidic flavor precursors present in diverse food and beverage products, we underscore the significance of glycosidases with various origins. Subsequently, we delve into emerging insights regarding the release of aroma within the human oral cavity due to the activity of oral microbial glycosidases.
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Glutathione transferases (GST) are detoxification enzymes that conjugate glutathione to a wide array of molecules. In the honey bee Apis mellifera, AmGSTD1 is the sole member of the delta class of GSTs, with expression in antennae. Here, we structurally and biochemically characterized AmGSTD1 to elucidate its function. We showed that AmGSTD1 can efficiently catalyse the glutathione conjugation of classical GST substrates. Additionally, AmGSTD1 exhibits binding properties with a range of odorant compounds. AmGSTD1 has a peculiar interface with a structural motif we propose to call 'sulfur sandwich'. This motif consists of a cysteine disulfide bridge sandwiched between the sulfur atoms of two methionine residues and is stabilized by CH S hydrogen bonds and S S sigma-hole interactions. Thermal stability studies confirmed that this motif is important for AmGSTD1 stability and, thus, could facilitate its functions in olfaction.
Assuntos
Glutationa Transferase , Glutationa , Abelhas , Animais , Glutationa Transferase/metabolismo , Catálise , Glutationa/metabolismo , EnxofreRESUMO
Oxidoreductases are major enzymes of xenobiotic metabolism. Consequently, they are essential in the chemoprotection of the human body. Many xenobiotic metabolism enzymes have been shown to be involved in chemosensory tissue protection. Among them, some were additionally shown to be involved in chemosensory perception, acting in signal termination as well as in the generation of metabolites that change the activation pattern of chemosensory receptors. Oxidoreductases, especially aldehyde dehydrogenases and aldo-keto reductases, are the first barrier against aldehyde compounds, which include numerous odorants. Using a mass spectrometry approach, we characterized the most highly expressed members of these families in the human nasal mucus sampled in the olfactory vicinity. Their expression was also demonstrated using immunohistochemistry in human epitheliums sampled in the olfactory vicinity. Recombinant enzymes corresponding to three highly expressed human oxidoreductases (ALDH1A1, ALDH3A1, AKR1B10) were used to demonstrate the high enzymatic activity of these enzymes toward aldehyde odorants. The structureâfunction relationship set based on the enzymatic parameters characterization of a series of aldehyde odorant compounds was supported by the X-ray structure resolution of human ALDH3A1 in complex with octanal.
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Oxirredutases , Receptores Odorantes , Humanos , Oxirredutases/metabolismo , Odorantes/análise , Xenobióticos/metabolismo , Olfato/fisiologia , Sistema Respiratório/metabolismo , Oxirredutases do Álcool/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismoRESUMO
Glutathione transferases (GSTs) are ubiquitous key enzymes with different activities as transferases or isomerases. As key detoxifying enzymes, GSTs are expressed in the chemosensory organs. They fulfill an essential protective role because the chemosensory organs are located in the main entry paths of exogenous compounds within the body. In addition to this protective function, they modulate the perception process by metabolizing exogenous molecules, including tastants and odorants. Chemosensory detection involves the interaction of chemosensory molecules with receptors. GST contributes to signal termination by metabolizing these molecules. By reducing the concentration of chemosensory molecules before receptor binding, GST modulates receptor activation and, therefore, the perception of these molecules. The balance of chemoperception by GSTs has been shown in insects as well as in mammals, although their chemosensory systems are not evolutionarily connected. This review will provide knowledge supporting the involvement of GSTs in chemoperception, describing their localization in these systems as well as their enzymatic capacity toward odorants, sapid molecules, and pheromones in insects and mammals. Their different roles in chemosensory organs will be discussed in light of the evolutionary advantage of the coupling of the detoxification system and chemosensory system through GSTs.
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Glutationa Transferase , Mamíferos , Animais , Glutationa Transferase/metabolismo , Mamíferos/metabolismo , Ligação Proteica , Insetos/metabolismo , Glutationa/metabolismoRESUMO
Glutathione transferases are detoxification enzymes with multifaceted roles, including a role in the metabolism and scavenging of nitric oxide (NO) compounds in cells. Here, we explored the ability of Trametes versicolor glutathione transferases (GSTs) from the Omega class (TvGSTOs) to bind metal-nitrosyl compounds. TvGSTOs have been studied previously for their ligandin role and are interesting models to study proteinâligand interactions. First, we determined the X-ray structure of the TvGSTO3S isoform bound to the dinitrosyl glutathionyl iron complex (DNGIC), a physiological compound involved in the storage of nitric oxide. Our results suggested a different binding mode compared to the one previously described in human GST Pi 1 (GSTP1). Then, we investigated the manner in which TvGSTO3S binds three nonphysiological metal-nitrosyl compounds with different metal cores (iron, ruthenium and osmium). We assayed sodium nitroprusside, a well-studied vasodilator used in cases of hypertensive crises or heart failure. Our results showed that the tested GST can bind metal-nitrosyls at two distinct binding sites. Thermal shift analysis with six isoforms of TvGSTOs identified TvGSTO6S as the best interactant. Using the Griess method, TvGSTO6S was found to improve the release of nitric oxide from sodium nitroprusside in vitro, whereas the effects of human GST alpha 1 (GSTA1) and GSTP1 were moderate. Our results open new structural perspectives for understanding the interactions of glutathione transferases with metal-nitrosyl compounds associated with the biochemical mechanisms of NO uptake/release in biological systems.
Assuntos
Óxido Nítrico , Trametes , Humanos , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Trametes/metabolismo , Glutationa Transferase/metabolismo , Ferro/metabolismo , Glutationa/metabolismoRESUMO
Flavor perception is a key factor in the acceptance or rejection of food. Aroma precursors such as cysteine conjugates are present in various plant-based foods and are metabolized into odorant thiols in the oral cavity. To date, the involved enzymes are unknown, despite previous studies pointing out the likely involvement of carbon-sulfur lyases (C-S lyases) from the oral microbiota. In this study, we show that saliva metabolizes allyl-cysteine into odorant thiol metabolites, with evidence suggesting that microbial pyridoxal phosphate-dependent C-S lyases are involved in the enzymatic process. A phylogenetic analysis of PatB C-S lyase sequences in four oral subspecies of Fusobacterium nucleatum was carried out and led to the identification of several putative targets. FnaPatB1 from F. nucleatum subspecies animalis, a putative C-S lyase, was characterized and showed high activity with a range of cysteine conjugates. Enzymatic and X-ray crystallographic data showed that FnaPatB1 metabolizes cysteine derivatives within a unique active site environment that enables the formation of flavor sulfur compounds. Using an enzymatic screen with a library of pure compounds, we identified several inhibitors able to reduce the C-S lyase activity of FnaPatB1 in vitro, which paves the way for controlling the release of odorant sulfur compounds from their cysteine precursors in the oral cavity.
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Liases , Compostos de Enxofre , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismo , Cisteína/metabolismo , Fusobacterium nucleatum , Liases/genética , Liases/metabolismo , Filogenia , Compostos de Sulfidrila/metabolismo , Compostos de Enxofre/metabolismoRESUMO
Glutathione transferases (GSTs) are ubiquitous enzymes that catalyze the conjugation of glutathione to various molecules. Among the 42 GSTs identified in Drosophila melanogaster, Delta and Epsilon are the largest classes, with 25 members. The Delta and Epsilon classes are involved in different functions, such as insecticide resistance and ecdysone biosynthesis. The insect GST number variability is due mainly to these classes. Thus, they are generally considered supports during the evolution for the adaptability of the insect species. To explore the link between Delta and Epsilon GST and their evolution, we analyzed the sequences using bioinformatic tools. Subgroups appear within the Delta and Epsilon GSTs with different levels of diversification. The diversification also appears in the sequences showing differences in the active site. Additionally, amino acids essential for structural stability or dimerization appear conserved in all GSTs. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that the transcripts corresponding to these two classes are heterogeneously expressed within D. melanogaster. Some GSTs, such as GSTD1, are highly expressed in all tissues, suggesting their general function in detoxification. Conversely, some others, such as GSTD11 or GSTE4, are specifically expressed at a high level specifically in antennae, suggesting a potential role in olfaction.
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Within the peripheral olfactory process, odorant metabolizing enzymes are involved in the active biotransformation of odorants, thus influencing the intensity and quality of the signal, but little evidence exists in humans. Here, we characterized the fast nasal metabolism of the food aroma pentane-2,3-dione in vivo and identified two resulting metabolites in the nasal-exhaled air, supporting the metabolizing role of the dicarbonyl/l-xylulose reductase. We showed in vitro, using the recombinant enzyme, that pentane-2,3-dione metabolism was inhibited by a second odorant (e.g., butanoic acid) according to an odorant-odorant competitive metabolic mechanism. Hypothesizing that such mechanism exists in vivo, pentane-2,3-dione, presented with a competitive odorant, both at subthreshold concentrations, was actually significantly perceived, suggesting an increase in its nasal availability. Our results, suggesting that odorant metabolizing enzymes can balance the relative detection of odorants in a mixture, in turn influencing the intensity of the signal, should be considered to better manage flavor perception in food.
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Odorantes , Receptores Odorantes , Humanos , Pentanos , Receptores Odorantes/metabolismo , OlfatoRESUMO
The molecules that elicit taste sensation are perceived by interacting with the taste receptors located in the taste buds. Enzymes involved in the detoxification processes are found in saliva as well as in type II cells, where taste receptors, including bitter taste receptors, are located. These enzymes are known to interact with a large panel of molecules. To explore a possible link between these enzymes and bitter taste perception, we demonstrate that salivary glutathione transferases (GSTA1 and GSTP1) can metabolize bitter molecules. To support these abilities, we solve three X-ray structures of these enzymes in complexes with isothiocyanates. Salivary GSTA1 and GSTP1 are expressed in a large panel of subjects. Additionally, GSTA1 levels in the saliva of people suffering from taste disorders are significantly lower than those in the saliva of the control group.
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Papilas Gustativas , Paladar , Humanos , Saliva/química , Percepção GustatóriaRESUMO
The oral cavity is an entry path into the body, enabling the intake of nutrients but also leading to the ingestion of harmful substances. Thus, saliva and oral tissues contain enzyme systems that enable the early neutralization of xenobiotics as soon as they enter the body. Based on recently published oral proteomic data from several research groups, this review identifies and compiles the primary detoxification enzymes (also known as xenobiotic-metabolizing enzymes) present in saliva and the oral epithelium. The functions and the metabolic activity of these enzymes are presented. Then, the activity of these enzymes in saliva, which is an extracellular fluid, is discussed with regard to the salivary parameters. The next part of the review presents research evidencing oral metabolization of aroma compounds and the putative involved enzymes. The last part discusses the potential role of these enzymatic reactions on the perception of aroma compounds in light of recent pieces of evidence of in vivo oral metabolization of aroma compounds affecting their release in mouth and their perception. Thus, this review highlights different enzymes appearing as relevant to explain aroma metabolism in the oral cavity. It also points out that further works are needed to unravel the effect of the oral enzymatic detoxification system on the perception of food flavor in the context of the consumption of complex food matrices, while considering the impact of food oral processing. Thus, it constitutes a basis to explore these biochemical mechanisms and their impact on flavor perception.
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Odorantes , Proteoma , Boca , Proteômica , SalivaRESUMO
Flavor perception during food intake is one of the main drivers of food acceptability and consumption. Recent studies have pointed to the oral microbiota as an important factor modulating flavor perception. This review introduces general characteristics of the oral microbiota, factors potentially influencing its composition, as well as known relationships between oral microbiota and chemosensory perception. We also review diverse evidenced mechanisms enabling the modulation of chemosensory perception by the microbiota. They include modulation of the chemosensory receptors activation by microbial metabolites but also modification of receptors expression. Specific enzymatic reactions catalyzed by oral microorganisms generate fragrant molecules from aroma precursors in the mouth. Interestingly, these reactions also occur during the processing of fermented beverages, such as wine and beer. In this context, two groups of aroma precursors are presented and discussed, namely, glycoside conjugates and cysteine conjugates, which can generate aroma compounds both in fermented beverages and in the mouth. The two entailed families of enzymes, i.e., glycosidases and carbon-sulfur lyases, appear to be promising targets to understand the complexity of flavor perception in the mouth as well as potential biotechnological tools for flavor enhancement or production of specific flavor compounds.
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Flavor is one of the main drivers of food consumption and acceptability. It is associated with pleasure feels during eating. Flavor is a multimodal perception corresponding to the functional integration of information from the chemical senses: olfaction, gustation, and nasal and oral somatosensory inputs. As a result, astringency, as a sensation mediated by the trigeminal nerves, influences food flavor. Despite the importance of astringency in food consumer acceptance, the exact chemosensory mechanism of its detection and the nature of the receptors activated remain unknown. Herein, after reviewing the current hypotheses on the molecular origin of astringency, we proposed a ground-breaking hypothesis on the molecular mechanisms underpinning this sensation as a perspective for future research.
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Adstringentes , Sensação , Aromatizantes , Aditivos Alimentares , PaladarRESUMO
The Omega class of glutathione transferases (GSTs) forms a distinct class within the cytosolic GST superfamily because most of them possess a catalytic cysteine residue. The human GST Omega 1 isoform was first characterized twenty years ago, but it took years of work to clarify the roles of the human isoforms. Concerning the kingdom of fungi, little is known about the cellular functions of Omega glutathione transferases (GSTOs), although they are widely represented in some of these organisms. In this study, we re-assess the phylogeny and the classification of GSTOs based on 240 genomes of mushroom-forming fungi (Agaricomycetes). We observe that the number of GSTOs is not only extended in the order of Polyporales but also in other orders such as Boletales. Our analysis leads to a new classification in which the fungal GSTOs are divided into two Types A and B. The catalytic residue of Type-A is either cysteine or serine, while that of Type-B is cysteine. The present study focuses on Trametes versicolor GSTO isoforms that possess a catalytic cysteine residue. Transcriptomic data show that Type-A GSTOs are constitutive enzymes while Type-B are inducible ones. The crystallographic analysis reveals substantial structural differences between the two types while they have similar biochemical profiles in the tested conditions. Additionally, these enzymes have the ability to bind antioxidant molecules such as wood polyphenols in two possible binding sites as observed from X-ray structures. The multiplication of GSTOs could allow fungal organisms to adapt more easily to new environments.
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Agaricales/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Variação Genética , Glutationa Transferase/química , Glutationa Transferase/genética , Filogenia , Agaricales/química , Agaricales/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Proteínas Fúngicas/classificação , Proteínas Fúngicas/metabolismo , Glutationa Transferase/classificação , Glutationa Transferase/metabolismo , Modelos Moleculares , Conformação ProteicaRESUMO
Xenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites). Enzymes, such as cytochrome P450 and glutathione transferases (GSTs), have been proposed to participate in odorant clearance in insects and mammals as odorant metabolizing enzymes. This study aims to explore the function of GSTs in human olfaction. Using immunohistochemical methods, GSTs were found to be localized in human tissues surrounding the olfactory epithelium. Then, the activity of 2 members of the GST family toward odorants was measured using heterologously expressed enzymes. The interactions/reactions with odorants were further characterized using a combination of enzymatic techniques. Furthermore, the structure of the complex between human GSTA1 and the glutathione conjugate of an odorant was determined by X-ray crystallography. Our results strongly suggest the role of human GSTs in the modulation of odorant availability to ORs in the peripheral olfactory process.
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Glutationa Transferase/metabolismo , Odorantes , Mucosa Olfatória/metabolismo , Glutationa Transferase/análise , HumanosRESUMO
In plants, tetrapyrrole biosynthesis occurs in chloroplasts, the reactions being catalysed by stromal and membrane-bound enzymes. The tetrapyrrole moiety is a backbone for chlorophylls and cofactors such as sirohaems, haems and phytochromobilins. Owing to this diversity, the potential cytotoxicity of some precursors and the associated synthesis costs, a tight control exists to adjust the demand and the fluxes for each molecule. After synthesis, haems and phytochromobilins are incorporated into proteins found in other subcellular compartments. However, there is only very limited information about the chaperones and membrane transporters involved in the trafficking of these molecules. After summarizing evidence indicating that glutathione transferases (GST) may be part of the transport and/or degradation processes of porphyrin derivatives, we provide experimental data indicating that tau glutathione transferases (GSTU) bind protoporphyrin IX and haem moieties and use structural modelling to identify possible residues responsible for their binding in the active site hydrophobic pocket. Finally, we discuss the possible roles associated with the binding, catalytic transformation (i.e. glutathione conjugation) and/or transport of tetrapyrroles by GSTUs, considering their subcellular localization and capacity to interact with ABC transporters. This article is part of the theme issue 'Retrograde signalling from endosymbiotic organelles'.