Proteomics

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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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Publications

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 (H<sub>2</sub>S) is a cytoprotective redox-active metabolite that signals through protein persulfidation (R-SS<sub>n</sub>H). 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 H<sub>2</sub>S production. We hypothesize that dietary restriction (DR), which increases lifespan and can boost H<sub>2</sub>S production, expands  ...[more]

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