Dataset Information

Dietary restriction transforms the mammalian protein sulfhydrome in a tissue-specific and cystathionine γ-lyase-dependent manner

ABSTRACT: Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation on relatively few identified proteins, tissue-specific sulfhydrome profiles and their associated functions are not well characterized, specifically under conditions known to modulate H2S production. We hypothesized that dietary restriction (DR), which increases lifespan and can boost H2S production, expands tissue-specific sulfhydromes. Here, we found protein persulfidation was enriched in liver, kidney, muscle, and brain but decreased in heart of young and aged male mice under two forms of DR, with DR promoting persulfidation in numerous metabolic and aging-related pathways. Mice lacking H2S producing enzyme cystathionine γ-lyase (CGL) had overall decreased tissue protein persulfidation and failed to functionally augment sulfhydromes in response to DR. Overall, we defined tissue- and CGL-dependent sulfhydromes and how diet transforms their makeup, underscoring the breadth for DR and H2S to impact biological processes and organismal health.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Posterior Adductor Muscle, Heart, Brain, Blood Plasma, Liver, Kidney

SUBMITTER: Nazmin Bithi

LAB HEAD: Christopher Hine

PROVIDER: PXD022954 | Pride | 2021-01-25

REPOSITORIES: Pride

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			Action	DRS
	AgedBrainAL1Lum_19oct1401.raw	Raw
	AgedBrainAL2Lum_19oct1402.raw	Raw
	AgedBrainAL3Lum_19oct1403.raw	Raw
	AgedBrainAL4Lum_19oct1404.raw	Raw
	AgedBrainAL5Lum_19oct1405.raw	Raw

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Dietary restriction transforms the mammalian protein persulfidome in a tissue-specific and cystathionine γ-lyase-dependent manner.

Bithi Nazmin N Link Christopher C Henderson Yoko O YO Kim Suzie S Yang Jie J Li Ling L Wang Rui R Willard Belinda B Hine Christopher C

Nature communications 20210319 1

Hydrogen sulfide (H2S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SSnH). Despite the known importance of persulfidation, tissue-specific persulfidome profiles and their associated functions are not well characterized, specifically under conditions and interventions known to modulate H2S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H2S production, expands ...[more]

PMID: 33741971

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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.