4.8 Article

Reduced mitochondria provide an essential function for the cytosolic methionine cycle

Journal

CURRENT BIOLOGY
Volume 32, Issue 23, Pages 5057-+

Publisher

CELL PRESS
DOI: 10.1016/j.cub.2022.10.028

Keywords

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Funding

  1. European Research Council (ERC) under the European Union [771592]
  2. Grant Agency of Charles University [1162320]
  3. Ministry of Education, Youth and Sports (MEYS) of the Czech Republic [CZ.02.1.01/0.0/0.0/16_019/0000759]
  4. MEYS CR [LM2018129, e-INFRA CZ LM2018140]
  5. ERDF [CZ.02.1.01/0.0/0.0/18_046/0016045]
  6. European Research Council (ERC) [771592] Funding Source: European Research Council (ERC)

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The loss of mitochondria in oxymonad protists is related to the redirection of the essential Fe-S cluster assembly to the cytosol. However, as our understanding of diverse free-living protists expands, the list of functions of their mitochondrial-related organelles (MROs) also expands. By accurately analyzing the proteome of the MRO in Paratrimastix pyriformis, a close relative of oxymonads, we discovered another function, which involves the production of folate derivatives with one-carbon units and formate. These derivatives are likely to be used by the cytosolic methionine cycle.
The loss of mitochondria in oxymonad protists has been associated with the redirection of the essential Fe-S cluster assembly to the cytosol. Yet as our knowledge of diverse free-living protists broadens, the list of functions of their mitochondrial-related organelles (MROs) expands. We revealed another such function in the closest oxymonad relative, Paratrimastix pyriformis, after we solved the proteome of its MRO with high accuracy, using localization of organelle proteins by isotope tagging (LOPIT). The newly assigned enzymes connect to the glycine cleavage system (GCS) and produce folate derivatives with one-carbon units and formate. These are likely to be used by the cytosolic methionine cycle involved in S-adenosyl methionine recycling. The data provide consistency with the presence of the GCS in MROs of free-living species and its absence in most endobionts, which typically lose the methionine cycle and, in the case of oxymonads, the mitochondria.

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