ArticleResearch square2024
Mitochondrial RNA cytosolic leakage drives the SASP.
Stella Victorelli, Madeline Eppard, Seung-Hwa Woo, Stacia P A Everts, Helene Martini, Nicholas Pirius, Ana Catarina Franco, Yeaeun Han, Dominik Saul, Patrick L Splinter and 7 more
Abstract readPreprint
In one paragraphArticle in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
17 authors.
Stella VictorelliDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-5573-8019 Madeline EppardDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Seung-Hwa WooDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0002-9336-4457 Stacia P A EvertsDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Helene MartiniDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Nicholas PiriusDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Ana Catarina FrancoDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Yeaeun HanDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Dominik SaulRobert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.ORCID 0000-0002-0673-3710 Patrick L SplinterDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Steven P O'HaraDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Diana JurkDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0003-4486-0857 João F PassosDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.ORCID 0000-0001-8765-1890 Funding
Targeting Cellular Senescence to Extend HealthspanP01AG062413 · NIA · MAYO CLINIC ROCHESTER · PI Sundeep Khosla · 2019 to 2026
$28.7MPILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2MPathophysiology of Biliary DiseaseR01DK057993 · NIDDK · MAYO CLINIC ROCHESTER · PI LARUSSO, NICHOLAS F., O'HARA, STEVEN P · 2001 to 2025
$7.1MPathobiology of Nonalcoholic SteatohepatitisR01DK130884 · NIDDK · MAYO CLINIC ROCHESTER · PI Petra Hirsova · 2021 to 2026
$2.5MThe role of sub-lethal mitochondrial apoptotic stress in cellular senescenceR01AG068048 · NIA · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2020 to 2024
$2.2MDevelopment of machine learning software to quantitatively map telomere induced senescence in tissue sections during agingUH3CA268103 · NCI · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2023 to 2025
$1.6MInvestigating the role of cytosolic mitochondrial double-stranded RNA in cellular senescence and agingR01AG082708 · NIA · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2023 to 2025
$1.5MDevelopment of machine learning software to quantitatively map telomere induced senescence in tissue sections during agingUG3CA268103 · NCI · MAYO CLINIC ROCHESTER · PI PASSOS, JOAO · 2021 to 2022
$1.1MFast super-resolution/confocal microscopy for GI cell biologyS10OD028633 · OD · MAYO CLINIC ROCHESTER · PI MC NIVEN, MARK A. · 2021 to 2021
$600kNCI NIH HHS UG3 CA268103NCI NIH HHS UH3 CA268103NIA NIH HHS P01 AG062413NIA NIH HHS R01 AG068048NIA NIH HHS R01 AG082708NIDDK NIH HHS P30 DK084567NIDDK NIH HHS R01 DK057993NIDDK NIH HHS R01 DK130884NIH HHS S10 OD028633
6 · The paper itselfAbstract
Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction. Inhibition of these RNA sensors significantly reduces SASP factors. Furthermore, BAX and BAK plays a key role in mtRNA leakage during senescence, and their deletion diminishes SASP expression
Identifiers
PMID39257994
PMCPMC11384804
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