Proteomics

Dataset Information

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Modelling mitochondrial SAM depletion in fruit flies and mice


ABSTRACT: S-adenosylmethionine (SAM) is the principle biological methyl group donor for a diverse range of substrates. It is synthesised in the cytosolic methionine cycle and shuttled throughout the cell. The mitochondrial SAM (mitoSAM) pool depends on import through the inner-membrane SAMC and supports the maturation of metabolites and mitochondrial RNAs. Mutations in SAMC in patients cause a severe metabolic crisis, however, the organellar regulation of mitoSAM and the protein methylation landscape within mitochondria are largely unknown. Using fly and mouse models, we demonstrate that titrating mitoSAM differentially effects mitochondrial function. Metabolite and iron-sulfur cluster biosynthesis are disrupted due to acutely decreased methylation potential, while prolonged mitoSAM deficiency affects fly longevity and OXPHOS stability. The herein uploaded raw data was used for total larvae and total cell proteome quantification in the established lines. Our results define the critical role of cytoplasmic SAM production for mitochondrial methylation events and highlight the indirect effect of one-carbon metabolism on cellular bioenergetics.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly) Mus Musculus (mouse)

TISSUE(S): Larva, Embryonic Stem Cell

DISEASE(S): Inherited Metabolic Disorder

SUBMITTER: Florian Schober  

LAB HEAD: Anna Wredenberg

PROVIDER: PXD019550 | Pride | 2021-02-22

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
180406_QE_IA_NL_FS_160.raw Raw
180406_QE_IA_NL_FS_161.raw Raw
180406_QE_IA_NL_FS_162.raw Raw
180406_QE_IA_NL_FS_163.raw Raw
180406_QE_IA_NL_FS_164.raw Raw
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Publications


Induction of the one-carbon cycle is an early hallmark of mitochondrial dysfunction and cancer metabolism. Vital intermediary steps are localized to mitochondria, but it remains unclear how one-carbon availability connects to mitochondrial function. Here, we show that the one-carbon metabolite and methyl group donor <i>S</i>-adenosylmethionine (SAM) is pivotal for energy metabolism. A gradual decline in mitochondrial SAM (mitoSAM) causes hierarchical defects in fly and mouse, comprising loss of  ...[more]

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