ArticleThe Journal of biological chemistry2015
Sequential actions of SIRT1-RELB-SIRT3 coordinate nuclear-mitochondrial communication during immunometabolic adaptation to acute inflammation and sepsis.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
90 citing papers in PubMed, 136 citations in OpenAlex.
- α7-nAChR Activation is Associated with Attenuation of Cardiac Fibrosis in Ischemic Cardiomyopathy via SIRT3-Dependent Modulation of EndMT.Journal of cardiovascular translational research · 2026Article
- Review
- SIRT2 Regulates EX VIVO PBMC Adhesion in Septic Shock Patients.Shock (Augusta, Ga.) · 2026Article
- Targeting the immuno-inflammatory-microbial network: a key strategy for sepsis treatment.Frontiers in immunology · 2025Review
- Article
- Post-translational modifications in sepsis-induced organ dysfunction: mechanisms and implications.Frontiers in immunology · 2024Review
- Sirtuins in kidney homeostasis and disease: where are we now?Frontiers in endocrinology · 2024Review
- The role and therapeutic potential of SIRTs in sepsis.Frontiers in immunology · 2024Review
- Restoring the infected powerhouse: Mitochondrial quality control in sepsis.Redox biology · 2023Review
- Article
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- NADAntioxidants (Basel, Switzerland) · 2023Review
- Changes in hemoglobin oxidation and band 3 during blood storage impact oxygen sensing and mitochondrial bioenergetic pathways in the human pulmonary arterial endothelial cell model.Frontiers in physiology · 2023Article
- Advances in the Study of Immunosuppressive Mechanisms in Sepsis.Journal of inflammation research · 2023Review
- Fusobacterium nucleatum promotes the development of acute liver failure by inhibiting the NADGut pathogens · 2022Article
- Sirtuin1 attenuates acute liver failure by reducing reactive oxygen speciesWorld journal of gastroenterology · 2022Article
- SIRT3 regulates bronchial epithelium apoptosis and aggravates airway inflammation in asthma.Molecular medicine reports · 2022Article
- PDIA2 Bridges Endoplasmic Reticulum Stress and Metabolic Reprogramming During Malignant Transformation of Chronic Colitis.Frontiers in oncology · 2022Article
- SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure.Frontiers in immunology · 2022Article
- Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways.Antioxidants (Basel, Switzerland) · 2021Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
We reported that NAD(+)-dependent SIRT1, RELB, and SIRT6 nuclear proteins in monocytes regulate a switch from the glycolysis-dependent acute inflammatory response to fatty acid oxidation-dependent sepsis adaptation. We also found that disrupting SIRT1 activity during adaptation restores immunometabolic homeostasis and rescues septic mice from death. Here, we show that nuclear SIRT1 guides RELB to differentially induce SIRT3 expression and also increases mitochondrial biogenesis, which alters bioenergetics during sepsis adaptation. We constructed this concept using TLR4-stimulated THP1 human promonocytes, a model that mimics the initiation and adaptation stages of sepsis. Following increased expression, mitochondrial SIRT3 deacetylase activates the rate-limiting tricarboxylic acid cycle (TCA) isocitrate dehydrogenase 2 and superoxide dismutase 2, concomitant with increases in citrate synthase activity. Mitochondrial oxygen consumption rate increases early and decreases during adaptation, parallel with modifications to membrane depolarization, ATP generation, and production of mitochondrial superoxide and whole cell hydrogen peroxide. Evidence of SIRT1-RELB induction of mitochondrial biogenesis included increases in mitochondrial mass, mitochondrial-to-nuclear DNA ratios, and both nuclear and mitochondrial encoded proteins. We confirmed the SIRT-RELB-SIRT3 adaptation link to mitochondrial bioenergetics in both TLR4-stimulated normal and sepsis-adapted human blood monocytes and mouse splenocytes. We also found that SIRT1 inhibition ex vivo reversed the sepsis-induced changes in bioenergetics.
Indexed as
Identifiers
What OpenQuestion holds
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.