Doke 2023 Nat Metab

From Bioblast
Publications in the MiPMap
Doke T, Mukherjee S, Mukhi D, Dhillon P, Abedini A, Davis JG, Chellappa K, Chen B, Baur JA, Susztak K (2023) NAD+ precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury. https://doi.org/10.1038/s42255-023-00761-7

Β» Nat Metab 5:414-30. PMID: 36914909 Open Access

Doke Tomohito, Mukherjee Sarmistha, Mukhi Dhanunjay, Dhillon Poonam, Abedini Amin, Davis James G, Chellappa Karthikeyani, Chen Beishan, Baur Joseph A, Susztak Katalin (2023) Nat Metab

Abstract: Our understanding of how global changes in cellular metabolism contribute to human kidney disease remains incompletely understood. Here we show that nicotinamide adenine dinucleotide (NAD+) deficiency drives mitochondrial dysfunction causing inflammation and kidney disease development. Using unbiased global metabolomics in healthy and diseased human kidneys, we identify NAD+ deficiency as a disease signature. Furthermore using models of cisplatin- or ischaemia-reperfusion induced kidney injury in male mice we observed NAD+ depletion Supplemental nicotinamide riboside or nicotinamide mononucleotide restores NAD+ levels and improved kidney function. We find that cisplatin exposure causes cytosolic leakage of mitochondrial RNA (mtRNA) and activation of the cytosolic pattern recognition receptor retinoic acid-inducible gene I (RIG-I), both of which can be ameliorated by restoring NAD+. Male mice with RIG-I knock-out (KO) are protected from cisplatin-induced kidney disease. In summary, we demonstrate that the cytosolic release of mtRNA and RIG-I activation is an NAD+-sensitive mechanism contributing to kidney disease.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US PA Philadelphia Baur JA


Labels: MiParea: Respiration, Genetic knockout;overexpression, mt-Medicine  Pathology: Other 

Organism: Human  Tissue;cell: Kidney  Preparation: Isolated mitochondria 

Regulation: Redox state  Coupling state: OXPHOS  Pathway: N, CIV  HRR: Oxygraph-2k 

2023-03 

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