ArticleCirculation. Heart failure2015
Tumor necrosis factor receptor-associated factor 2 mediates mitochondrial autophagy.
Article in Circulation. Heart failure, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.
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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function.Circulation research · 2026Article
- Disrupted Mitochondrial Quality Control in Atherosclerotic Disease: Mitophagy and Dynamics in Focus.JACC. Basic to translational science · 2026Review
- Mastering cardiomyocyte mitophagy: molecular governance, pathological derailment and therapeutics.PeerJ · 2026Review
- Mitochondrial quality control in cardiomyocytes: safeguarding the heart against disease and ageing.Nature reviews. Cardiology · 2025Review
- Mitochondrial quality control as a therapeutic target in cardiovascular disease: Mechanistic insights and future directions.Journal of translational internal medicine · 2025Article
- Inflammation and cancer cell survival: TRAF2 as a key player.Cell death & disease · 2025Review
- Predicting Which Mitophagy Proteins Are Dysregulated in Spinocerebellar Ataxia Type 3 (SCA3) Using the Auto-p2docking Pipeline.International journal of molecular sciences · 2025Article
- Article
- Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy.Circulation research · 2024Article
- Perillaldehyde Functions as a Potential Antifungal Agent by Triggering Metacaspase-Independent Apoptosis in Botrytis cinerea.Microbiology spectrum · 2023Article
- Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications.Cell biology and toxicology · 2023Review
- Cardiovascular hemodynamics in mice with tumor necrosis factor receptor-associated factor 2 mediated cytoprotection in the heart.Frontiers in cardiovascular medicine · 2023Article
- The protein kinase R modifies gut physiology to limit colitis.Frontiers in immunology · 2023Article
- Diversity of mitophagy pathways at a glance.Journal of cell science · 2022Article
- Article
- Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy.Circulation · 2022Article
- Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTumor necrosis factor (TNF) signaling protects against ischemia/reperfusion-induced cardiomyocyte death, in vitro, ex vivo, and in vivo. TNF-receptor-associated factor 2 (TRAF2), an E3 ubiquitin ligase, coordinates cytoprotective signaling downstream of both TNF receptors, via unclear mechanisms. Noting that TRAF2 is recruited to mitochondria, and that autophagic removal of ubiquitin-tagged damaged mitochondria is cytoprotective, we tested the hypothesis that TRAF2 mediates mitochondrial autophagy. METHODS AND
resultsTRAF2 localizes to the mitochondria in neonatal rat cardiac myocytes, and TNF treatment transcriptionally upregulates TRAF2 abundance in the mitochondrial subfraction. TRAF2 colocalizes with ubiquitin, p62 adaptor protein, and mitochondria within LC3-bound autophagosomes; and exogenous TRAF2 enhances autophagic removal of mitochondria. TRAF2 knockdown with adenoviral shRNA transduction induces accumulation of depolarized mitochondria in resting neonatal rat cardiac myocytes, as well as in those treated with TNF or uncoupling agent carbonyl cyanide m-chlorophenyl hydrazone, suggesting an essential role for TRAF2 in homeostatic and stress-induced mitochondrial autophagy. TRAF2 also colocalizes and interacts with PARKIN, a previously described E3 ubiquitin ligase and mitophagy effector, on depolarized mitochondria in neonatal rat cardiac myocytes. Exogenous expression of TRAF2, but not its E3 ligase-deficient mutants, is sufficient to partially restore mitophagy in the setting of PARKIN knockdown, suggesting redundancy in their ubiquitin ligase roles. TRAF2 abundance increases in the mitochondrial subfraction of ischemia/reperfusion-modeled hearts; and exogenous TRAF2, but not its E3 ligase-deficient mutants, reduces depolarized mitochondria and rescues cell death in neonatal rat cardiac myocytes subjected to hypoxia/reoxygenation.
conclusionsTaken together, these data indicate an essential role for TRAF2 in concert with PARKIN as a mitophagy effector, which contributes to TRAF2-induced cytoprotective signaling.
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.