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Updated: Aug 5, 2026
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Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Pannexin1 promotes cellular senescence by triggering mtDNA release to activate the cGAS-STING pathway
Jiaqi Li1, Xin Zhao1, Yanting Shen1
1Nanfang Hospital, Southern Medical University, Guangzhou, China; National Clinical Research Center for Kidney and Urological Diseases, Nanfang Hospital, Guangzhou, China; State Key Laboratory of Multi-organ Injury Prevention and Treatment, Guangzhou, China; Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou, China; Guangdong Provincial Institute of Nephrology, Guangzhou, China.
Summary
Pannexin 1 (Panx1) channels drive kidney disease progression by releasing mitochondrial DNA, activating the cGAS-STING pathway, and promoting cellular senescence. Blocking this pathway alleviates kidney damage and fibrosis.
Area of Science:
- Nephrology
- Cell Biology
- Immunology
Background:
- Cellular senescence drives acute kidney injury (AKI) to chronic kidney disease (CKD) transition.
- Pannexin 1 (Panx1) channels promote renal tubular senescence, but downstream effectors are unknown.
Purpose of the Study:
- To elucidate the downstream signaling pathway of Panx1 in promoting renal tubular senescence.
- To establish a mechanistic link between Panx1 and the cGAS-STING pathway.
Main Methods:
- Investigated Panx1-mediated mitochondrial DNA release and cGAS-STING pathway activation.
- Utilized genetic and pharmacological inhibition of the Panx1-mPTP-BAX-cGAS cascade.
- Employed mouse models of renal ischemia/reperfusion injury.
Main Results:
- Panx1 triggers cGAS-STING activation via mitochondrial permeability transition pore (mPTP) opening, BAX translocation, and subsequent mitochondrial DNA (mtDNA) release.
- Cytosolic mtDNA activates cGAS-STING, inducing senescence-associated secretory phenotype (SASP) via NF-κB and interferon responses via IRF3.
- Inhibition of Panx1 or STING attenuated senescence, fibrosis, and AKI to CKD progression in mice.
Conclusions:
- The Panx1/mPTP/BAX/cGAS-STING axis is a key driver of cellular senescence in kidney disease.
- Targeting this pathway offers potential therapeutic strategies for mitigating senescence-associated kidney pathologies.
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