Proteomics

Dataset Information

0

CLYBL averts methylmalonyl-CoA mutase inhibition and loss of vitamin B12 by repairing malyl-CoA


ABSTRACT: Citrate lyase beta-like protein (CLYBL) is a ubiquitously expressed mammalian enzyme known for its role in the degradation of itaconate, a bactericidal immunometabolite produced in activated macrophages. The association of CLYBL loss-of-function with reduced circulating vitamin B12 levels was proposed to result from inhibition of the B12-dependent enzyme methylmalonyl-CoA mutase (MCM) by itaconyl-CoA. The discrepancy between the highly inducible and locally confined production of itaconate and the broad expression profile of CLYBL across tissues, suggested a role for this enzyme beyond itaconate catabolism. We discovered that CLYBL additionally functions as a metabolite repair enzyme for malyl-CoA, a side-product of promiscuous TCA cycle enzymes. We found that CLYBL knockout cells, accumulating malyl-CoA but not itaconyl-CoA, show decreased levels of adenosylcobalamin and that malyl-CoA is a more potent inhibitor of MCM than itaconyl-CoA. Our work thus suggests that malyl-CoA plays a role in the B12 deficiency observed in individuals with CLYBL loss-of-function. Data deposited herein corresponds to the untargeted LC-HRMS/MS acyl-CoA ester and HILIC analyses conducted for this study.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Carole Linster  

PROVIDER: MSV000095949 | MassIVE |

REPOSITORIES: MassIVE

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2017-05-01 | E-GEOD-76850 | biostudies-arrayexpress
2017-05-01 | E-GEOD-76853 | biostudies-arrayexpress
2017-05-01 | GSE76853 | GEO
2017-05-01 | GSE76850 | GEO
2021-04-26 | GSE173256 | GEO
2022-08-05 | GSE203302 | GEO
2017-05-01 | GSE90854 | GEO
2017-05-01 | GSE90853 | GEO
2017-05-01 | GSE90855 | GEO
2013-11-21 | E-GEOD-47983 | biostudies-arrayexpress