The Potential Mechanism of D-Amino Acids - Mitochondria Axis in the Progression of Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM) and stands out as the leading cause of end-stage renal disease worldwide. There is increasing evidence that mitochondrial dysfunction, including impaired mitochondrial biogenesis, dynamics, and oxidative stress, contributes to the development and progression of DKD. D-amino acids (D-AAs), which are enantiomers of L-AAs, have recently been detected in various living organisms and are acknowledged to play important roles in numerous physiological processes in the human body. Accumulating evidence demonstrates that D-AA levels in blood or urine could serve as useful biomarkers for reflecting renal function. The physiological roles of D-AAs are implicated in the regulation of cellular proliferation, oxidative stress, generation of reactive oxygen species (ROS), and innate immunity. This article reviews current evidence relating to D-AAs and mitochondrial dysfunction and proposes a potential interaction and contribution of the D-AAs-mitochondria axis in DKD pathophysiology and progression. This insight could provide novel therapeutic approaches for preventing or ameliorating DKD based on this biological axis.

Keywords: D-amino acid; ROS production; diabetic kidney disease; gut microbiota; mitochondria; oxidative stress.

Figure 1

A potential biological interaction of D-AAs and mitochondria in DKD pathogenesis. AGEs, advanced glycation end products; ETC, electron transport chain; D-AA, D-amino acid; D-Ala, D-alanine; D-Arg, D-arginine; D-Cys, D-cysteine; D-Met, D-methionine; D-Tryp, D-tryptophan; D-Ser, D-serine; DAO, D-amino acid oxidase; DKD, diabetic kidney disease; NMDAR, N-methyl-d-aspartate receptors; ROS, reactive oxygen species; SOD, superoxide dismutase; 3MP, 3-mercaptopyruvate; 3MST, 3-mercaptopyruvate sulfurtransferase.