Disrupted Alpha-Ketoglutarate Homeostasis: Understanding Kidney Diseases from the View of Metabolism and Beyond

Abstract

Alpha-ketoglutarate (AKG) is a key intermediate of various metabolic pathways including tricarboxylic acid (TCA) cycle, anabolic and catabolic reactions of amino acids, and collagen biosynthesis. Meanwhile, AKG also participates in multiple signaling pathways related to cellular redox regulation, epigenetic processes, and inflammation response. Emerging evidence has shown that kidney diseases like diabetic nephropathy and renal ischemia/reperfusion injury are associated with metabolic disorders. In consistence with metabolic role of AKG, further metabolomics study demonstrated a dysregulated AKG level in kidney diseases. Intriguingly, earlier studies during the years of 1980s and 1990s indicated that AKG may benefit wound healing and surgery recovery. Recently, interests on AKG are arising again due to its protective roles on healthy ageing, which may shed light on developing novel therapeutic strategies against age-related diseases including renal diseases. This review will summarize the physiological and pathological properties of AKG, as well as the underlying molecular mechanisms, with a special emphasis on kidney diseases.

Keywords:

• alpha-ketoglutarate
• kidney diseases
• metabolism
• diabetic nephropathy
• acute kidney injury

Acknowledgments

The authors would like to thank the anonymous reviewers for their valuable comments and suggestions for improving the quality of the paper. This work was funded by the National Natural Science Foundation of China (No. 82100769), and Science and Technology Planning Project of Zhanjiang City (2021A05064).

Disclosure

The authors report no conflicts of interest in this work.