Alterations in Nucleocytoplasmic Localization of the Methionine Cycle Induced by Oxidative Stress During Liver Disease

Abstract Homeostasis of the main cellular methyl donor, S-adenosylmethionine, depends on the methionine cycle, which is at the crossroads of metabolic pathways involved in the synthesis and regulation of a large variety of compounds and processes. Impairment of the methionine cycle is detected in a vast majority of liver diseases that concur with oxidative stress. The complex regulation of the pathway is exerted from transcriptional to protein oligomerization and activity levels, subcellular distribution being recently added to the play. Oxidative stress performs a role at all of these regulatory levels either directly (e.g., eliciting protein modifications) or indirectly (e.g., decreasing recycling of vitamin B12). Therefore, the interest in deciphering the mechanisms through which medical interventions could revert methionine cycle impairment, contributing to liver disease treatment. In this line, the control of subcellular distribution has emerged as a putative target for new and existent antioxidants, their evaluation requiring a large research effort.