Dataset Information

Methyl-SILAF mapping of the Drosophila mitochondrial protein methylome

ABSTRACT: S-adenosylmethionine (SAM) is the principal 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 S-adenosylmethionine carrier (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. We developed a fly-compatible SILAC labelling technique and mapped mitochondrial protein methylation sites in Drosophila melanogaster, further showing that SAM is the sole methyl group donor for these modifications, with no contribution from folate-species. This dataset comprises MS-runs used for quality control of methyl-SILAF, the methylome mapping and exclusion of folates as protein methyl-group donors.

INSTRUMENT(S): Orbitrap Fusion Lumos, Q Exactive HF

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Larva

SUBMITTER: Florian Schober

LAB HEAD: Anna Wredenberg

PROVIDER: PXD019654 | Pride | 2021-02-21

REPOSITORIES: Pride

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Publications

The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters.

Rosenberger Florian A FA Moore David D Atanassov Ilian I Moedas Marco F MF Clemente Paula P Végvári Ákos Á Fissi Najla El NE Filograna Roberta R Bucher Anna-Lena AL Hinze Yvonne Y The Matthew M Hedman Erik E Chernogubova Ekaterina E Begzati Arjana A Wibom Rolf R Jain Mohit M Nilsson Roland R Käll Lukas L Wedell Anna A Freyer Christoph C Wredenberg Anna A

Science advances 20210219 8

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]

PMID: 33608280

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Project description:Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. For carcinogenesis, a modified resistant hepatocyte model was used. Rats were initiated with diethylnitrosamine (DEN) (200 mg/kg of body weight) at day 0. Then, 2-acetylaminofluorene (AAF) was administered (20 mg/kg per dose) at days 7, 8 and 9, followed by 3/5 partial hepatectomy (PH) at day 10. Three control groups of non-treated animals were sacrificed by exsanguination on the first day and at 9 and 18 months after the beginning of the experiment. Treated animals were sacrificed at 1, 7, 11 and 16 days and at 1, 9 and 18 months. Their livers were excised, washed in physiological saline solution, frozen with liquid nitrogen in 2-methyl butane and stored at -80°C. Once selected and separately collected nodular, tumoral and its adjacent tissues, total RNA was isolated using TriPureIsolation Reagent (Roche) according to the manufacturer’s protocol. The microarray analysis was performed using GeneChip Rat Exon 1.0 ST Arrays. Four replicas for each condition and controls were analyzed. This created 11 pairwise contrasts for the differential expression analysis. We grouped all evaluated conditions in three categories: i) early stages, including samples obtained since day one until one month after treatment, these were compared against rats without treatment sacrificed the first day; ii) tumor, nodular and its adjacent tissues obtained from nine months rats were compared against rats without treatment of the same age; and iii) tumor and its adjacent tissues obtained from eighteen months rats were compared against rats without treatment of the same age.

Dataset Information

Methyl-SILAF mapping of the Drosophila mitochondrial protein methylome

Publications

The one-carbon pool controls mitochondrial energy metabolism via complex I and iron-sulfur clusters.

Similar Datasets

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