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Series GSE196610 Query DataSets for GSE196610
Status Public on Aug 16, 2023
Title Sub-lethal apoptotic stress enables mtDNA release during senescence and drives the SASP
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Senescent cells drive age-related tissue dysfunction partially via the induction of a chronic senescence-associated secretory phenotype (SASP). Mitochondria are major regulators of the SASP; however, the underlying mechanisms have not been elucidated. Mitochondria also control apoptosis, a cell fate generally perceived as distinct from cellular senescence, which is apoptosis resistant. Here, we show that mitochondrial outer membrane permeability (MOMP) occurring in a small subset of mitochondria is a feature of cellular senescence. This process, called minority MOMP (miMOMP), depends on the formation of BAX and BAK macropores and results in release of mitochondrial DNA (mtDNA) into the cytosol, which in turn activates the cGAS/STING pathway, a major regulator of the SASP. Importantly, we found that inhibition of MOMP in vivo decreases inflammatory markers and improves healthspan parameters in aged mice. Our results propose the novel concept that apoptosis and senescence are regulated by similar mitochondrial-dependent mechanisms, and that sub-lethal mitochondrial apoptotic stress is a major driver of the SASP. We also provide proof-of-concept that inhibition of miMOMP may be a new therapeutic avenue to improve healthspan.
 
Overall design mRNA profiles of senescent fibroblasts upon mitochondria clearance and following the re-introduction of mitochondrial DNA. We also examined the effects of Bax and Bak knockout on mRNA profile of proliferating and senescent fibroblasts.
 
Contributor(s) Victorelli S, Martini H, Vizioli MG, Lei X
Citation(s) 37821702
Submission date Feb 11, 2022
Last update date Dec 01, 2023
Contact name Xue Lei
E-mail(s) xlei@sbpdiscovery.org
Organization name SBP medical discovery institute
Lab Peter Adams Lab
Street address 10901 N Torrey Pines Rd
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (24)
GSM5896621 Human primary lung fibroblasts IMR90- Proliferating Parkin: Parkin_Prol_rep1
GSM5896622 Human primary lung fibroblasts IMR90- Proliferating Parkin: Parkin_Prol_rep2
GSM5896623 Human primary lung fibroblasts IMR90- Proliferating Parkin: Parkin_Prol_rep3
Relations
BioProject PRJNA806156

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Supplementary file Size Download File type/resource
GSE196610_fpkm.tsv.gz 3.5 Mb (ftp)(http) TSV
GSE196610_raw_count.tsv.gz 1.1 Mb (ftp)(http) TSV
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