TY - JOUR
T1 - Metabolic Rewiring and Communication
T2 - An Integrative View of Kidney Proximal Tubule Function
AU - Chrysopoulou, Maria
AU - Rinschen, Markus M
PY - 2024/2
Y1 - 2024/2
N2 - The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function (filtration, transport, secretion, and reabsorption), metabolite transformation, and metabolite signaling determine kidney metabolic rewiring in disease. Energy metabolism and substrates for key metabolic pathways are orchestrated by metabolite sensors. Given the importance of renal function for the inner milieu, we also review metabolic communication routes with other organs. Exciting research opportunities exist to understand metabolic perturbation of kidney and proximal tubule function, for example, in hypertension-associated kidney disease. We argue that, based on the integrative view outlined here, kidney diseases without genetic cause should be approached scientifically as metabolic diseases. Expected final online publication date for the
Annual Review of Physiology, Volume 86 is February 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
AB - The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function (filtration, transport, secretion, and reabsorption), metabolite transformation, and metabolite signaling determine kidney metabolic rewiring in disease. Energy metabolism and substrates for key metabolic pathways are orchestrated by metabolite sensors. Given the importance of renal function for the inner milieu, we also review metabolic communication routes with other organs. Exciting research opportunities exist to understand metabolic perturbation of kidney and proximal tubule function, for example, in hypertension-associated kidney disease. We argue that, based on the integrative view outlined here, kidney diseases without genetic cause should be approached scientifically as metabolic diseases. Expected final online publication date for the
Annual Review of Physiology, Volume 86 is February 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
KW - AKI
KW - CKD
KW - SGLT2
KW - amino acids
KW - diabetes
KW - fatty acid metabolism
KW - gluconeogenesis
KW - glycolysis
KW - ketone body metabolism
U2 - 10.1146/annurev-physiol-042222-024724
DO - 10.1146/annurev-physiol-042222-024724
M3 - Review
C2 - 38012048
SN - 0066-4278
VL - 86
SP - 405
EP - 427
JO - Annual Review of Physiology
JF - Annual Review of Physiology
ER -