Nutrient-sensing mTORC1 and AMPK pathways in chronic kidney diseases

Nat Rev Nephrol. 2023 Feb;19(2):102-122. doi: 10.1038/s41581-022-00648-y. Epub 2022 Nov 24.

Abstract

Nutrients such as glucose, amino acids and lipids are fundamental sources for the maintenance of essential cellular processes and homeostasis in all organisms. The nutrient-sensing kinases mechanistic target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are expressed in many cell types and have key roles in the control of cell growth, proliferation, differentiation, metabolism and survival, ultimately contributing to the physiological development and functions of various organs, including the kidney. Dysregulation of these kinases leads to many human health problems, including cancer, neurodegenerative diseases, metabolic disorders and kidney diseases. In the kidney, physiological levels of mTOR and AMPK activity are required to support kidney cell growth and differentiation and to maintain kidney cell integrity and normal nephron function, including transport of electrolytes, water and glucose. mTOR forms two functional multi-protein kinase complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Hyperactivation of mTORC1 leads to podocyte and tubular cell dysfunction and vulnerability to injury, thereby contributing to the development of chronic kidney diseases, including diabetic kidney disease, obesity-related kidney disease and polycystic kidney disease. Emerging evidence suggests that targeting mTOR and/or AMPK could be an effective therapeutic approach to controlling or preventing these diseases.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Mechanistic Target of Rapamycin Complex 2 / metabolism
  • Multiprotein Complexes / metabolism
  • Nutrients
  • Polycystic Kidney Diseases*
  • Renal Insufficiency, Chronic*
  • Signal Transduction / physiology
  • Sirolimus
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Mechanistic Target of Rapamycin Complex 1
  • AMP-Activated Protein Kinases
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 2
  • Sirolimus