Dataset Information

The mitochondrial methylome is evolutionary conserved and regulated by cytosolic SAM

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. We mapped mitochondrial protein methylation sites in Drosphila and, in a targeted screen, we find that methylated residues are highly conserved between fly, mouse and human. Unexpectedly, many methylation events occur outside of mitochondria, independent of the mitoSAM pool. 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): Orbitrap Fusion Lumos

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

TISSUE(S): Larva, Cell Culture, Embryonic Stem Cell, Fibroblast

DISEASE(S): Mitochondrial Metabolism Disease

SUBMITTER: Florian Schober

LAB HEAD: Anna Wredenberg

PROVIDER: PXD019494 | Pride | 2021-02-22

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20190705_L_03_Batch2_C1.raw	Raw
	20190705_L_04_Batch2_C2.raw	Raw
	20200110_L1_01_ES25cm_FS_PRM_Mm_1A.raw	Raw
	20200110_L1_02_ES25cm_FS_PRM_Mm_2A.raw	Raw
	20200110_L1_03_ES25cm_FS_PRM_Mm_1B.raw	Raw

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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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