Dataset Information

Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S- producing enzymes altering persulfidome composition

ABSTRACT: Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive disease driven byobesity-related hepatic inflammation and oxidative stress. Recently, cysteine persulfidation (PSSH), a protective post-translational modification by hydrogen sulfide (H2S), was established to play a role in redox regulation. Despite the role of the liver in H2S metabolism, the function of PSSH in MASH remains underexplored. We demonstrated that H2S-producingenzymes are downregulated in both human and mouse livers with steatosis and fibrosis, resulting in a decline in global PSSH levels. Surprisingly, dimedone-switch mass spectrometry in dietary mouse models of distinct obesity-associated liver disease stages revealed dysregulated PSSH on specific proteins. In particular, increased hepatic PSSH levels of proteintyrosine phosphatases and redox regulators were found in advanced disease stages, suggesting a targeted adaptive response to oxidative stress. Overall, our findings demonstrated that impaired H2S production disrupts protective PSSH networks in MASH. However, selective PSSH preservation on redox-sensitive proteins may represent a compensatory mechanism, underscoring the therapeutic potential of persulfidation in restoring redox homeostasis during obesity-associated chronic liver disease.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Thibaut Vignane

LAB HEAD: Milos Filipovic

PROVIDER: PXD066952 | Pride | 2025-09-15

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Eclipse_01483_Control_2.raw	Raw
	Eclipse_01484_HFD_2.raw	Raw
	Eclipse_01485_HFHFHCD_2.raw	Raw
	Eclipse_01486_CDHFD_2.raw	Raw
	Eclipse_01488_HFD_5.raw	Raw

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Publications

Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S-producing enzymes altering persulfidome composition.

Shen Tzu Keng TK Vignane Thibaut T Gilglioni Eduardo H EH Traini Leonardo L Kalaitsidou Elisavet E Conan Pierre P Li Ao A St-Pierre-Wijckmans Wadsen W Herranz Jose M JM Elvira Bernat B Otero Sanchez Lukas L Trépo Eric E Deelman Leo L Wu Wei W Filipovic Milos R MR Messens Joris J Ezeriņa Daria D Gurzov Esteban N EN

Redox biology 20250805

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease driven by obesity-related hepatic inflammation and oxidative stress. Recently, cysteine persulfidation (PSSH), a protective post-translational modification by hydrogen sulfide (H2S), was established to play a role in redox regulation. Despite the role of the liver in H2S metabolism, the function of PSSH in MASH remains underexplored. We demonstrated that H2S-producing enzymes are dow ...[more]

PMID: 40889425

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Project description:Hydrogen sulfide (H2S) is a signaling molecule that regulates essential plant processes, such as autophagy and responses to abiotic stresses. Although there is much information about the processes in which H2S is involved, the mechanism of action of H2S is still unclear. However, the posttranslational modification of cysteine residues, named persulfidation, is the main proposed mechanism. In this study, the role of H2S during drought that allows plant stress adaptation has been analyzed, with the focus on the underlying mechanism. H2S pretreatment before imposing drought on plants significantly improved phenotypic traits and decreased the content of biochemical and molecular drought stress markers. In addition, H2S regulated amino acid metabolism and repressed drought-induced degradation pathways, such as bulk autophagy and protein ubiquitination. The label-free quantitative proteomic analysis of plants growing under control and drought stress identified 887 proteins significantly different persulfidated between both conditions. Bioinformatic analyses revealed that the biological processes most enriched containing the proteins more persulfidated in drought corresponded to cellular response to oxidative stress, and hydrogen peroxide catabolism. In addition, protein degradation, abiotic stress responses, anthocyanin-containing compound biosynthetic process, and flavonoid biosynthesis were highlighted. On the contrary, the most enriched biological process containing proteins with lower levels of persulfidation in drought corresponded to the biosynthetic processes of glucosinolates and chlorophyll. Therefore, our findings emphasize the role of H2S as a promoter of enhanced tolerance to drought, enabling plants to respond more rapidly and efficiently after exposure to drought. Furthermore, the proteomic analysis supports the main role of protein persulfidation as the molecular mechanism of H2S to alleviate ROS accumulation and balance redox homeostasis under drought stress.

Project description:Hydrogen sulfide is an important signaling molecule in plants that regulates essential biological processes through protein persulfidation. Although numerous persulfidated proteins were found to be involved in photorespiration, little was known about sulfide-mediated regulation of photorespiration. Label-free quantitative proteomic analysis has revealed a high impact on the protein persulfidation level when plants grown under non-photorespiratory conditions are transferred to air, with the 97 % of total identified proteins more persulfidated under suppressed photorespiration. A detailed study of the effect of sulfide on important aspects associated with photorespiratory growth conditions has provided insight into the role of sulfide in protecting plants grown under suppressed photorespiration. In these conditions, sulfide amends the metabolic imbalance of carbon/nitrogen and restores ATP levels to concentrations similar to those in air grown conditions. Sulfide also plays an essential role in balancing the significant high level of ROS measured in plants under non-photorespiratory conditions to reach a similar cellular redox state in air-grown plants, through the regulation of antioxidative defenses. Furthermore, sulfide regulates another important characteristic resulting from suppression of photorespiration, such as the stomata closure, to decrease the high guard cell ROS levels and inducing the stomata aperture. In this way, sulfide signals the movement of the CO2-dependent stomata to achieve a scenario similar to that of plants growing under normal air conditions, in the opposite direction of the already established ABA-dependent movement of the stomata. Therefore, our findings suggest that the high persulfidation level under suppressed photorespiration reveals an essential role of sulfide signaling under these conditions, and with respect to stomatal movement, the outcome of this signaling is dependent on the growth/stress condition under study.

Dataset Information

Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S- producing enzymes altering persulfidome composition

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Metabolic dysfunction-associated steatohepatitis reduces hepatic H<sub>2</sub>S-producing enzymes altering persulfidome composition.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Metabolic dysfunction-associated steatohepatitis reduces hepatic H2S- producing enzymes altering persulfidome composition

Dataset's files

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Metabolic dysfunction-associated steatohepatitis reduces hepatic H&lt;sub&gt;2&lt;/sub&gt;S-producing enzymes altering persulfidome composition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Metabolic dysfunction-associated steatohepatitis reduces hepatic H<sub>2</sub>S-producing enzymes altering persulfidome composition.