<i>Caenorhabditis elegans</i> methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor.

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 <i>Caenorhabditis elegans,</i> 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 <i>nhr-10</i> 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 <i>nhr-114</i> to activate Met/SAM cycle gene expression, the vitamin B12 transporter, <i>pmp-5</i>, and adjust influx and efflux of the cycle by activating <i>msra-1</i> and repressing <i>cbs-1</i>, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.