ArticleNucleic acids research2022
Mitochondrial stress induces AREG expression and epigenomic remodeling through c-JUN and YAP-mediated enhancer activation.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
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- Integrative Multi-Analysis Identifies METTL3-Regulated FGF19 and H6PD as Candidate Targets in Diabetic Cognitive Impairment.Biomolecules · 2026Article
- Smarca4 maintains mitochondrial homeostasis and energy metabolism during cardiac development.Cellular and molecular life sciences : CMLS · 2026Article
- Bioinformatics And Experimental Insights Into Sotorasib Resistance Mechanisms in Non-small-cell Lung Cancer.Anti-cancer agents in medicinal chemistry · 2026Article
- Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis.Frontiers in medicine · 2026Review
- Yes-associated protein 1 in cancer: bridging mechanical transduction and epigenetic regulation.Cancer biology & therapy · 2025Review
- Microbiota, mitochondria, and epigenetics in health and disease: converging pathways to solve the puzzle.Pflugers Archiv : European journal of physiology · 2025Review
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.International journal of biological sciences · 2024Article
- Mitochondrial complex III deficiency drives c-MYC overexpression and illicit cell cycle entry leading to senescence and segmental progeria.Nature communications · 2023Article
- Lactic acidosis induces metabolic and phenotypic reprogramming in cholangiocarcinoma cells via the upregulation of thrombospondin-1.Cancer science · 2023Article
- MYC-an emerging player in mitochondrial diseases.Frontiers in cell and developmental biology · 2023Review
- Brown adipose tissue-derived exosomes delay fertility decline in aging mice.Frontiers in endocrinology · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleus-mitochondria crosstalk is essential for cellular and organismal homeostasis. Although anterograde (nucleus-to-mitochondria) pathways have been well characterized, retrograde (mitochondria-to-nucleus) pathways remain to be clarified. Here, we found that mitochondrial dysfunction triggered a retrograde signaling via unique transcriptional and chromatin factors in hepatic cells. Our transcriptomic analysis revealed that the loss of mitochondrial transcription factor A led to mitochondrial dysfunction and dramatically induced expression of amphiregulin (AREG) and other secretory protein genes. AREG expression was also induced by various mitochondria stressors and was upregulated in murine liver injury models, suggesting that AREG expression is a hallmark of mitochondrial damage. Using epigenomic and informatic approaches, we identified that mitochondrial dysfunction-responsive enhancers of AREG gene were activated by c-JUN/YAP1/TEAD axis and were repressed by chromatin remodeler BRG1. Furthermore, while mitochondrial dysfunction-activated enhancers were enriched with JUN and TEAD binding motifs, the repressed enhancers possessed the binding motifs for hepatocyte nuclear factor 4α, suggesting that both stress responsible and cell type-specific enhancers were reprogrammed. Our study revealed that c-JUN and YAP1-mediated enhancer activation shapes the mitochondrial stress-responsive phenotype, which may shift from metabolism to stress adaptation including protein secretion under such stressed conditions.
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