ArticleNature communications2024
Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed.
- Senescence-independent SASP drives tumor-macrophage inflammatory cascade and therapeutic resistance in HNSCC.Functional & integrative genomics · 2026Article
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Role of Pattern Recognition Receptors (PRRs) in Spinal Cord Injury (SCI): A Comprehensive Review.Molecular neurobiology · 2026Review
- Tumour-associated dsRNA accumulation and innate immune activation: mechanistic basis and therapeutic strategies.EBioMedicine · 2026Review
- PRMT5-mediated intron retention triggers innate and adaptive immunity against cancer.EMBO molecular medicine · 2026Article
- Mitochondrial RNA-Type I Interferon Axis in Sjögren's Disease: Molecular Mechanisms and Translational Implications.International journal of molecular sciences · 2026Review
- LC-MS/MS Profiling of Blood Serum Reveals Disease-Enriched Peptides in Metabolic Syndrome.Journal of personalized medicine · 2026Article
- Interferon-λ drives renal fibrosis by coordinating epithelial-fibroblast crosstalk.The Journal of experimental medicine · 2026Article
- An Ultrastructural and Proteomic Analysis in DM1 Young Adults' Myoblasts: Stressed RER and Mitochondrial Dysfunction Involvement.Journal of cellular and molecular medicine · 2026Article
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- A spatial multi-omics atlas of immunosenescence reveals germinal-center B cell dysfunction in human lymph nodes.Cell press blue · 2026Article
- Disruption of macrophage migration inhibitory factor signaling induces major tumor-associated macrophage phenotypes in human M2 macrophages.Molecular biomedicine · 2026Article
- Mitochondrial ncRNAs: From Pathological Regulation to Targeted Therapy in Cardiovascular Diseases.Journal of cardiovascular translational research · 2026Review
- Article
- Review
- Transcriptomic Evidence of Mitochondrial Double-Stranded RNA Accumulation in Brain Aging and Alzheimer's Disease.Aging cell · 2026Article
- Immunological consequences of senescence in physiology and pathology.Journal of translational medicine · 2026Review
- Senescent cells in systemic aging: SASP heterogeneity, immune escape, and endocrine modulation.Biogerontology · 2026Review
- Mitochondrial double-stranded RNA fuels pancreatic cancer growth via RIG-I/TLR3 inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
Corrections and comments
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9 authors.
Funding
Abstract
The escape of mitochondrial double-stranded dsRNA (mt-dsRNA) into the cytosol has been recently linked to a number of inflammatory diseases. Here, we report that the release of mt-dsRNA into the cytosol is a general feature of senescent cells and a critical driver of their inflammatory secretome, known as senescence-associated secretory phenotype (SASP). Inhibition of the mitochondrial RNA polymerase, the dsRNA sensors RIGI and MDA5, or the master inflammatory signaling protein MAVS, all result in reduced expression of the SASP, while broadly preserving other hallmarks of senescence. Moreover, senescent cells are hypersensitized to mt-dsRNA-driven inflammation due to their reduced levels of PNPT1 and ADAR1, two proteins critical for mitigating the accumulation of mt-dsRNA and the inflammatory potency of dsRNA, respectively. We find that mitofusin MFN1, but not MFN2, is important for the activation of the mt-dsRNA/MAVS/SASP axis and, accordingly, genetic or pharmacologic MFN1 inhibition attenuates the SASP. Finally, we report that senescent cells within fibrotic and aged tissues present dsRNA foci, and inhibition of mitochondrial RNA polymerase reduces systemic inflammation associated to senescence. In conclusion, we uncover the mt-dsRNA/MAVS/MFN1 axis as a key driver of the SASP and we identify novel therapeutic strategies for senescence-associated diseases.
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