ArticleNature2016
PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 341 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
341 citing papers in PubMed, 526 citations in OpenAlex.
- Randomized crossover clinical trial of coenzyme Q10 and nicotinamide riboside in chronic kidney disease.JCI insight · 2023Trial
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- SOCS2 Downregulation Is Associated with a Ferro-Aging-Related Transcriptomic Signature in Proximal Tubular Cells in Chronic Kidney Disease.Biomedicines · 2026Article
- Poria cocos Polysaccharides Protect Against Contrast-Induced Renal Injury Through Activating CaMKK2/AMPK/PGC-1α Signaling Pathway.Phytotherapy research : PTR · 2026Article
- Spatial analysis reveals cellular microenvironments and mechanisms of inflammation and injury in acute interstitial nephritis.Nature communications · 2026Article
- Redox-Mediated Mitochondrial Dysfunction as a Common Pathogenic Axis in Acute Kidney Injury and Chronic Kidney Disease.Biomolecules · 2026Review
- Rewiring the mitochondrial NADMaterials today. Bio · 2026Article
- Purine-Metabolism Reprogramming Associated with Failed-Repair Proximal Tubule States in the AKI-to-CKD Transition.Metabolites · 2026Article
- Review
- Organelle Crosstalk in Renal Cells: Insights from Cell Biology and Implications for AKI-to-CKD Transition.International journal of molecular sciences · 2026Review
- AHR: The Overlooked Mediator in SkincareBridging Environmental Sensing and Skin Physiology.Environment & health (Washington, D.C.) · 2026Review
- Single-cell Stereo-seq reveals regulatory mechanisms driving regeneration of injured proximal tubules during AKI.Nature communications · 2026Article
- Effects of NAD⁺ repletion with Nicotinamide riboside on obesity-induced chronic kidney disease and renal cell lipotoxicity.Scientific reports · 2026Article
- AMPK is dispensable for physiological podocyte and glomerular functions but prevents glomerular fibrosis in experimental diabetes.Cell death discovery · 2026Article
- Integrating metabolomics and machine learning with in silico analysis to identify early biomarkers and molecular interactions in sepsis-associated acute kidney injury.Scientific reports · 2026Article
- Pyruvate Dehydrogenase and Cellular Metabolism in Calcineurin Inhibitor-Induced Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2026Article
- Early-activated extracellular matrix proteins shape the metabolic and spatial dynamics of the kidney fibrotic microenvironment.Nature metabolism · 2026Article
- Lipids in kidney diseases: from systemic imbalance to intrarenal alterations of cellular lipid metabolism in rare and common kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2026Review
- The Influence of Sex and Hormones on Organelle Stress in Kidney Injury: Insights from Preclinical Models.Biology · 2026Review
- Targeted PGC-1α gene delivery by GV-assisted ultrasound cavitation for renal ischemia-reperfusion injury therapy.iScience · 2026Article
281 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
The energetic burden of continuously concentrating solutes against gradients along the tubule may render the kidney especially vulnerable to ischaemia. Acute kidney injury (AKI) affects 3% of all hospitalized patients. Here we show that the mitochondrial biogenesis regulator, PGC1α, is a pivotal determinant of renal recovery from injury by regulating nicotinamide adenine dinucleotide (NAD) biosynthesis. Following renal ischaemia, Pgc1α(-/-) (also known as Ppargc1a(-/-)) mice develop local deficiency of the NAD precursor niacinamide (NAM, also known as nicotinamide), marked fat accumulation, and failure to re-establish normal function. Notably, exogenous NAM improves local NAD levels, fat accumulation, and renal function in post-ischaemic Pgc1α(-/-) mice. Inducible tubular transgenic mice (iNephPGC1α) recapitulate the effects of NAM supplementation, including more local NAD and less fat accumulation with better renal function after ischaemia. PGC1α coordinately upregulates the enzymes that synthesize NAD de novo from amino acids whereas PGC1α deficiency or AKI attenuates the de novo pathway. NAM enhances NAD via the enzyme NAMPT and augments production of the fat breakdown product β-hydroxybutyrate, leading to increased production of prostaglandin PGE2 (ref. 5), a secreted autacoid that maintains renal function. NAM treatment reverses established ischaemic AKI and also prevented AKI in an unrelated toxic model. Inhibition of β-hydroxybutyrate signalling or prostaglandin production similarly abolishes PGC1α-dependent renoprotection. Given the importance of mitochondrial health in ageing and the function of metabolically active organs, the results implicate NAM and NAD as key effectors for achieving PGC1α-dependent stress resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.