Difference between revisions of "Doke 2023 Nat Metab"
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{{Publication | {{Publication | ||
|title=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 | |title=Doke T, Mukherjee S, Mukhi D, Dhillon P, Abedini A, Davis JG, Chellappa K, Chen B, Baur JA, Susztak K (2023) NAD<sup>+</sup> precursor supplementation prevents mtRNA/RIG-I-dependent inflammation during kidney injury. https://doi.org/10.1038/s42255-023-00761-7 | ||
|info=Nat Metab | |info=Nat Metab 5:414-30. [https://www.ncbi.nlm.nih.gov/pubmed/36914909 PMID: 36914909 Open Access] | ||
|authors=Doke | |authors=Doke Tomohito, Mukherjee Sarmistha, Mukhi Dhanunjay, Dhillon Poonam, Abedini Amin, Davis James G, Chellappa Karthikeyani, Chen Beishan, Baur Joseph A, Susztak Katalin | ||
|year=2023 | |year=2023 | ||
|journal=Nat Metab | |journal=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. | |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<sup>+</sup>) deficiency drives mitochondrial dysfunction causing inflammation and kidney disease development. Using unbiased global metabolomics in healthy and diseased human kidneys, we identify NAD<sup>+</sup> deficiency as a disease signature. Furthermore using models of cisplatin- or ischaemia-reperfusion induced kidney injury in male mice we observed NAD<sup>+</sup> depletion Supplemental nicotinamide riboside or nicotinamide mononucleotide restores NAD<sup>+</sup> 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<sup>+</sup>. 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<sup>+</sup>-sensitive mechanism contributing to kidney disease. | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=US PA Philadelphia Baur JA | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Genetic knockout;overexpression, mt-Medicine | ||
|diseases=Other | |||
|organism=Human | |||
|tissues=Kidney | |||
|preparations=Isolated mitochondria | |||
|topics=Redox state | |||
|couplingstates=OXPHOS | |||
|pathways=N, CIV | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2023-03 | |additional=2023-03 | ||
}} | }} |
Latest revision as of 15:41, 19 December 2023
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