{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE291nnn/GSE291671/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Caenorhabditis elegans"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291671"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan in C. elegans","description":"Mild mitochondrial stress could extend lifespan across species, yet the underlying mechanism remains unclear. Here we show that inhibition of mitochondrial respiration induces a sustained transcriptional program that enhances lysosomal proteolysis during aging in Caenorhabditis elegans. Mechanistically, this response is primarily regulated by the intestinal GATA transcription factor ELT-2, which retains high expression and directly binds to GATA motifs in the promoters of lysosomal protease genes to promote their transcriptional activation. Moreover, we identified R249 within the conserved zinc-finger DNA-binding domain of ELT-2 as a key residue required for its transcriptional activity. Notably, this mitochondrion-ELT-2-lysosome axis operates largely independently of the mitochondrial unfolded protein response (UPRmt) to counteract aging. Furthermore, increased lysosomal activity, as well as the lysosomal proteases CPR-5 and CPR-8, are essential for mitochondrial stress-induced clearance of toxic polyglutamine (polyQ) aggregates and lifespan extension. Together, our findings reveal a previously unrecognized ELT-2-dependent lysosomal proteostasis pathway that acts downstream of mitochondrial stress to maintain protein homeostasis and promote longevity.","dates":{"publication":"2026/05/15"},"accession":"GSE291671","cross_references":{"GSM":["GSM8839609","GSM8839607","GSM8839629","GSM8839608","GSM8839627","GSM8839605","GSM8839628","GSM8839606","GSM8839625","GSM8839626","GSM8839623","GSM8839624","GSM8839621","GSM8839622","GSM8839620","GSM8839640","GSM8839618","GSM8839619","GSM8839616","GSM8839638","GSM8839639","GSM8839617","GSM8839636","GSM8839614","GSM8839637","GSM8839615","GSM8839634","GSM8839612","GSM8839613","GSM8839635","GSM8839610","GSM8839632","GSM8839633","GSM8839611","GSM8839630","GSM8839631"],"GPL":["25145"],"GSE":["291671"],"taxon":["Caenorhabditis elegans"]}}