ArticleCell discovery2016
HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression.
Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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
23 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The impact of mitochondrial impairments on sperm function and male fertility: a systematic review.Reproductive biology and endocrinology : RB&E · 2024Pooled it
- Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications.Research (Washington, D.C.) · 2026Review
- Aging through the lens of mitochondrial DNA mutations and inheritance paradoxes.Biogerontology · 2024Review
- Role of Heterogeneous Nuclear Ribonucleoproteins in the Cancer-Immune Landscape.International journal of molecular sciences · 2023Review
- Impact of the m.13513G>A Variant on the Functions of the OXPHOS System and Cell Retrograde Signaling.Current issues in molecular biology · 2023Article
- Investigation of embelin synthetic hybrids as potential COVID-19 and COX inhibitors: Synthesis, spectral analysis, DFT calculations and molecular docking studies.Journal of molecular structure · 2023Article
- Therapeutic potential of pyrrole and pyrrolidine analogs: an update.Molecular diversity · 2022Review
- Nuclear-Mitochondrial Interactions.Biomolecules · 2022Review
- hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease.Biology · 2021Review
- Roles of mitochondria in the hallmarks of metastasis.British journal of cancer · 2021Review
- The HNRNPA2B1-MST1R-Akt axis contributes to epithelial-to-mesenchymal transition in head and neck cancer.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Alcohol-induced CYP2E1, mitochondrial dynamics and retrograde signaling in human hepatic 3D organoids.Free radical biology & medicine · 2020Article
- Mitochondrial DNA copy number can influence mortality and cardiovascular disease via methylation of nuclear DNA CpGs.Genome medicine · 2020Article
- Thinking outside the nucleus: Mitochondrial DNA copy number in health and disease.Mitochondrion · 2020Review
- Mitochondria as intracellular signaling platforms in health and disease.The Journal of cell biology · 2020Review
- A New Rat Model of Chronic Cerebral Hypoperfusion Resulting in Early-Stage Vascular Cognitive Impairment.Frontiers in aging neuroscience · 2020Article
- Esophageal 3D organoids ofOncotarget · 2019Article
- Flavonoids: New Frontier for Immuno-Regulation and Breast Cancer Control.Antioxidants (Basel, Switzerland) · 2019Review
- Mitochondrial Retrograde Signalling and Metabolic Alterations in the Tumour Microenvironment.Cells · 2019Review
- More than a powerplant: the influence of mitochondrial transfer on the epigenome.Current opinion in physiology · 2018Article
Corrections and comments
- Erratum issuedCorrection to: HnRNPA2 is a novel histone acetyltransferase that mediates mitochondrial stress-induced nuclear gene expression.2019 · Klein Szanto A [corrected to Klein-Szanto AJ]
Authors and funding
17 authors.
Funding
Abstract
Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced transcription coactivator hnRNAP2 acetylates Lys 8 of H4 through an intrinsic histone lysine acetyltransferase (KAT) activity with Arg 48 and Arg 50 of hnRNAP2 being essential for acetyl-CoA binding and acetyltransferase activity. H4K8 acetylation at the mitochondrial stress-responsive promoters by hnRNAP2 is essential for transcriptional activation. We found that the previously described mitochondria-to-nucleus retrograde signaling-mediated transformation of C2C12 cells caused an increased expression of genes involved in various oncogenic processes, which is retarded in hnRNAP2 silenced or hnRNAP2 KAT mutant cells. Taken together, these data show that altered gene expression by mitochondria-to-nucleus retrograde signaling involves a novel hnRNAP2-dependent epigenetic mechanism that may have a role in cancer and other pathologies.
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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.