Amino acid metabolism and autophagy in skeletal development and homeostasis.

Abstract Bone is an active organ that is continuously remodeled throughout life via formation and resorption; therefore, a fine-tuned bone (re)modeling is crucial for bone homeostasis and is closely connected with energy metabolism. Amino acids are essential for various cellular functions as well as an energy source, and their synthesis and catabolism (e.g., metabolism of carbohydrates and fatty acids) are regulated through numerous enzymatic cascades. In addition, the intracellular levels of amino acids are maintained by autophagy, a cellular recycling system for proteins and organelles; under nutrient deprivation conditions, autophagy is strongly induced to compensate for cellular demands and to restore the amino acid pool. Metabolites derived from amino acids are known to be precursors of bioactive molecules such as second messengers and neurotransmitters, which control various cellular processes, including cell proliferation, differentiation, and homeostasis. Thus, amino acid metabolism and autophagy are tightly and reciprocally regulated in our bodies. This review discusses the current knowledge and potential links between bone diseases and deficiencies in amino acid metabolism and autophagy.