ArticleScience advances2022
FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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
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.
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Who cites it
41 citing papers in PubMed, 44 citations in OpenAlex.
- Unraveling the role of FGF21 in epilepsy disease: mechanistic insights and therapeutic Potential.Metabolic brain disease · 2026Review
- CLPP loss confers sex-specific protection from renal ischemia reperfusion injury.Redox biology · 2026Article
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- Adaptation of OXPHOS biogenesis to cellular requirements.Protein science : a publication of the Protein Society · 2026Review
- A multilayered stress-response circuit: The mammalian mitochondrial UPR.The FEBS journal · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Association between serum methylmalonic acid and metabolic dysfunction-associated steatotic liver disease: NHANES-based study.Medicine · 2026Article
- AMC-F1 regulates mitochondria-autophagy crosstalk independent of nutrient stress.Nature communications · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
- Screening and Stratification Utility of GDF-15 and FGF-21 in Individuals Evaluated for Suspected Mitochondrial Disease: A Malaysian Cohort Study.Metabolites · 2026Article
- Decoding the mechanistic basis of liver-muscle communication in health and disease.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Radiation-induced autophagy regulates fibroblast mitochondrial metabolism and crosstalk with triple-negative breast cancer cells.Cell reports · 2026Article
- Mutant CHCHD10 disrupts cytochrome c oxidation and activates mitochondrial retrograde signaling.EMBO molecular medicine · 2026Article
- Platycodin D alleviates cardiac hypertrophy in the treatment of heart failure by inhibiting p53-dependent BCL-2/Bax/caspase-3 signaling pathway.Frontiers in pharmacology · 2026Article
- Mammalian mitohormesis: from mitochondrial stressors to organismal benefits.The EMBO journal · 2025Review
- Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia.International journal of molecular sciences · 2025Article
- Molecular Mediators of the Cardiac Benefits of Exercise.Circulation research · 2025Review
- Atf3 controls transitioning in female mitochondrial cardiomyopathy as identified by spatial and single-cell transcriptomics.Science advances · 2025Article
- Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians.Aging cell · 2025Article
- Treating metabolic dysfunction-associated steatohepatitis: The fat-trimming FGF21 approach.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
The mitochondrial integrated stress response (mitoISR) has emerged as a major adaptive pathway to respiratory chain deficiency, but both the tissue specificity of its regulation, and how mitoISR adapts to different levels of mitochondrial dysfunction are largely unknown. Here, we report that diverse levels of mitochondrial cardiomyopathy activate mitoISR, including high production of FGF21, a cytokine with both paracrine and endocrine function, shown to be induced by respiratory chain dysfunction. Although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of mitoISR. In the absence of FGF21, a large part of the metabolic adaptation to mitochondrial dysfunction (one-carbon metabolism, transsulfuration, and serine and proline biosynthesis) is strongly blunted, independent of the primary mitoISR activator ATF4. Collectively, our work highlights the complexity of mitochondrial stress responses by revealing the importance of the tissue specificity and dose dependency of mitoISR.
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.