The stress-responsive protein REDD1 and its pathophysiological functions

Regulated in development and DNA damage-response 1 (REDD1) is a stress-induced protein that controls various cellular functions, including metabolism, oxidative stress, autophagy, and cell fate, and contributes to the pathogenesis of metabolic and inflammatory disorders, neurodegeneration, and cancer. REDD1 usually exerts deleterious effects, including tumorigenesis, metabolic inflammation, neurodegeneration, and muscle dystrophy; however, it also exhibits protective functions by regulating multiple intrinsic cell activities through either an mTORC1-dependent or -independent mechanism. REDD1 typically regulates mTORC1 signaling, NF-& kappa;B activation, and cellular pro-oxidant or antioxidant activity by interacting with 14-3-3 proteins, I & kappa;B & alpha;, and thioredoxin-interacting protein or 75 kDa glucose-regulated protein, respectively. The diverse functions of REDD1 depend on cell type, cellular context, interaction partners, and cellular localization (e.g., mitochondria, endomembrane, or cytosol). Therefore, comprehensively understanding the molecular mechanisms and biological roles of REDD1 under pathophysiological conditions is of utmost importance. In this review, based on the published literature, we highlight and discuss the molecular mechanisms underlying the REDD1 expression and its actions, biological functions, and pathophysiological roles. The gene that codes for the REDD1 protein is activated by a variety of cellular stresses, including metabolic imbalance and DNA damage; REDD1's effect on various aspects of cellular activities contributes to the pathogenesis of many diseases. Researchers in South Korea led by Young-Myeong Kim at Kangwon National University, Chuncheon, review the cellular functions, molecular mechanisms, and disease-causing actions of REDD1. They assess the extensive evidence on the mechanisms by which REDD1 acts as a detrimental factor in serious conditions, including metabolic disorders, cancer, muscle atrophy, neurological diseases, and autoimmune diseases. However, some of the evidence is uncertain and controversial, and the involvement of REDD1 in disease may depend on complex interactions with other factors, meaning further research is needed to improve understanding. Drugs that regulate the activity of the REDD1 protein or its gene could have therapeutic potential.