Methionine/S-adenosylmethionine Cycle Activity is Sensed and Adjusted by a Nuclear Hormone Receptor

Overview

Journal Elife

Specialty Biology

Date 2020 Oct 5

PMID 33016879

Citations 27

Authors

Gabrielle E Giese

Melissa D Walker

Olga Ponomarova

Hefei Zhang

Xuhang Li

Gregory Minevich

Albertha Jm Walhout

Affiliations

Soon will be listed here.

Abstract

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires to activate Met/SAM cycle gene expression, the vitamin B12 transporter, , and adjust influx and efflux of the cycle by activating and repressing , respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.

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