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The reduction of elemental sulfur (S⁰) or polysulfide to sulfide constitutes a significant part of the natural geobiological sulfur cycle. However, little is known about the enzymes catalyzing sulfur reduction in sulfur-reducing bacteria. Recently, we found a novel multiheme-containing selenoprotein (MHSEP) from a sulfur-reducing deltaproteobacterium, Geobacter sulfurreducens PCA. MHSEP catalyzed the reduction of polysulfide and selenite by using methyl viologen as an artificial electron donor. Kinetic analysis revealed that polysulfide was an efficient substrate for the enzyme. MHSEP gene disruption in G. sulfurreducens led to significant decreases in sulfur reduction and sulfide production in an S⁰-supplemented medium. The 1.98 Å crystal structure of MHSEP revealed that MHSEP formed a tetramer, in which each protomer contained five c-type hemes. Four of the five hemes were arranged so that electrons were transferred from the solvent-accessible heme 1, through heme 2 and heme 3, to heme 4. The heme 4 was in close vicinity to the catalytic Sec325 and was axially coordinated by His and Cys unlike the other four bis-His ligated hemes, suggesting that heme 4 could be the active-site cofactor.

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Nicotinamide adenine dinucleotide (NAD⁺) is an essential co-factor mediating numerous redox reactions. NAD⁺ also serves as a substrate for poly(ADP-ribose) polymerase (PARP) and sirtuins, and it regulates various biological processes such as metabolism, DNA repair, gene expression, and stress responses. In living organisms, a balance between NAD⁺ production and its degradation determines NAD⁺ levels. Recently, a number of studies have demonstrated that NAD⁺ levels decline with age and that the deterioration of NAD⁺ metabolism promotes aging and aging-associated diseases, including metabolic diseases, neurodegenerative disease, and musculoskeletal diseases. Conversely, elevated NAD⁺ levels in tissues have been shown to exhibit beneficial effects on both physiological and pathological aging. Various approaches, such as the supplementation with NAD⁺ precursors, the activation of NAD⁺ biosynthetic pathways, and the inhibition of NAD⁺ degradation, have been used to increase NAD⁺ levels in tissues. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NNM) are orally bioavailable NAD⁺ precursors that have demonstrated beneficial effects on aging and aging-associated diseases in animal models and humans. In this review, the overview of NAD⁺ metabolism has been introduced and the recent knowledge about NAD⁺ metabolism in aging has been described.

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