{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE294nnn/GSE294929/"]},"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=GSE294929"],"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":"GSE294929","cross_references":{"GSM":["GSM8930529","GSM8930539","GSM8930528","GSM8930527","GSM8930538","GSM8930537","GSM8930526","GSM8930536","GSM8930525","GSM8930524","GSM8930546","GSM8930535","GSM8930534","GSM8930545","GSM8930523","GSM8930544","GSM8930533","GSM8930543","GSM8930532","GSM8930542","GSM8930531","GSM8930541","GSM8930530","GSM8930540"],"GPL":["25145"],"GSE":["294929"],"taxon":["Caenorhabditis elegans"]}}