Mitochondrial transport and metabolism of the major methyl donor and versatile cofactor S‐adenosylmethionine, and related diseases: A review^†

Abstract

S-adenosyl-L-methionine (SAM) is a coenzyme and the most commonly used methyl-group donor for the modification of metabolites, DNA, RNA and proteins. SAM biosynthesis and SAM regeneration from the methylation reaction product S-adenosyl-L-homocysteine (SAH) take place in the cytoplasm. Therefore, the intramitochondrial SAM-dependent methyltransferases require the import of SAM and export of SAH for recycling. Orthologous mitochondrial transporters belonging to the mitochondrial carrier family have been identified to catalyze this antiport transport step: Sam5p in yeast, SLC25A26 (SAMC) in humans, and SAMC1-2 in plants. In mitochondria SAM is used by a vast number of enzymes implicated in the following processes: the regulation of replication, transcription, translation, and enzymatic activities; the maturation and assembly of mitochondrial tRNAs, ribosomes and protein complexes; and the biosynthesis of cofactors, such as ubiquinone, lipoate, and molybdopterin. Mutations in SLC25A26 and mitochondrial SAM-dependent enzymes have been found to cause human diseases, which emphasizes the physiological importance of these proteins.

Harnessing enzyme cofactors and plant metabolism: an essential partnership

“…In plants, both methionine biosynthesis and SAM metabolism occur in the chloroplasts, whereas SAM biosynthesis occurs in the cytosol (Heidari et al., 2020; Monné et al., 2022; Ravanel et al., 2004). SAM transporters have been identified in mitochondria (Palmieri et al., 2006), plastids (Bouvier et al., 2006), and Golgi membranes (Temple et al., 2022) (Table 2).…”

“…SAM transporters have been identified in mitochondria (Palmieri et al., 2006), plastids (Bouvier et al., 2006), and Golgi membranes (Temple et al., 2022) (Table 2). In chloroplasts, SAM must be imported to exert its influence on the one‐carbon metabolism and as a substrate for the methylation of Rubisco and several other enzyme‐catalyzed reactions (Monné et al., 2022; Palmieri et al., 2006; Ravanel et al., 2004). In both chloroplasts and mitochondria, SAM provides methyl groups for the modification of DNA, RNA, and proteins (Palmieri et al., 2006), and in the Golgi apparatus, it is required for plant cell wall polysaccharide methylation (Temple et al., 2022).…”