Modulation of the subcellular levels of redox cofactors by Nudix hydrolases in chloroplasts

Chloroplasts are organelles that generate reactive oxygen species (ROS) through redox reactions during photosynthesis. It is now widely accepted that the redox state of the organelle is a crucial factor in determining various physiological activities in plants such as stress responsiveness and immunity. In the chloroplast, two important nucleotide cofactors, NADPH and flavin adenine dinucleotide (FAD), are well known to be indispensable for many redox reactions and therefore its normal function. The redox states and levels of NADP(H) in particular are crucial factors in ROS homeostasis in chloroplasts because of their roles as electron acceptors in photosynthetic electron transport and reducing equivalents for antioxidant systems. In contrast, FAD is the essential cofactor for enzymes involved in the biosynthesis and recycling of ascorbate, the most abundant antioxidant in plants, as well as for blue-light signaling and photosynthesis. Thus, the metabolisms of these redox cofactors must be tightly regulated. The Nudix (Nucleoside diphosphate linked to some other moiety X) hydrolases (NUDXs) are a protein family that possesses pyrophosphohydrolase activity toward a wide variety of nucleoside diphosphate derivatives including the cofactors NAD(P)H and FAD. Arabidopsis thaliana possesses 28 NUDXs (AtNUDX1-27 and DCP2), which are divided into three groups based on their intracellular localization (i.e., cytosol, chloroplast, and mitochondrion). Of these, it has been demonstrated that AtNUDX19 regulates the intracellular levels and redox status of NADPH in the chloroplast and is involved in photosynthesis as well as stress and hormonal responses. AtNUDX23 participates in maintenance of the balance between FAD and flavin mononucleotide (FMN) levels by feedback regulation of the metabolism of flavins in the chloroplast. This review summarizes the physiological roles of NUDX enzymes as modulators of the subcellular levels of redox cofactors which can affect plant stress responses and physiological processes, and introduces recent progress in the studies of NUDXs in various organisms.