ArticleNature2011
Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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.
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Who cites it
93 citing papers in PubMed, 153 citations in OpenAlex.
- Single-Nucleotide Polymorphisms in Genes Associated with Mitochondrial and DNA Damage Response Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Humans.International journal of molecular sciences · 2026Article
- Human Endonuclease G Preferentially Cleaves Oxidatively Damaged DNA.Biochemistry · 2026Article
- Endonuclease G restores lipid homeostasis in spontaneously hypertensive rats: implications for mitochondrial function.Frontiers in physiology · 2026Article
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Mammalian TatD DNase domain containing 1 (TATDN1) is a proteostasis-responsive gene with roles in ventricular structure and neuromuscular function.The FEBS journal · 2025Article
- Mitochondria‑derived peptides: Promising microproteins in cardiovascular diseases (Review).Molecular medicine reports · 2025Review
- Endonuclease G promotes hepatic mitochondrial respiration by selectively increasing mitochondrial tRNAProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Probing the importance of AIF interaction with endonuclease G in mitochondrial inheritance and neurodegeneration.Cell discovery · 2024Article
- Reply to: The effects of ENDOG on lipid metabolism may be tissue-dependent and may not require its translocation from mitochondria.Nature communications · 2024Article
- The effects of ENDOG on lipid metabolism may be tissue-dependent and may not require its translocation from mitochondria.Nature communications · 2024Article
- Mitochondrial DNA release and sensing in innate immune responses.Human molecular genetics · 2024Review
- Article
- Systems genetics approaches for understanding complex traits with relevance for human disease.eLife · 2023Review
- Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress.Nature communications · 2023Article
- Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder.International journal of molecular sciences · 2023Article
- SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.Cell biology and toxicology · 2023Article
- Apoptotic proteins with non-apoptotic activity: expression and function in cancer.Apoptosis : an international journal on programmed cell death · 2023Review
- Nuclear endonuclease G controls cell proliferation in ovarian cancer.FEBS open bio · 2023Article
- Biochemical Mechanisms beyond Glycosphingolipid Accumulation in Fabry Disease: Might They Provide Additional Therapeutic Treatments?Journal of clinical medicine · 2023Review
- Proteomics analysis in myocardium of spontaneously hypertensive rats.Scientific reports · 2023Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 15 institutions in 7 countries.
Funding
Abstract
Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.
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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.