ArticleBMC biology2018
Mitochondrial unfolded protein response transcription factor ATFS-1 promotes longevity in a long-lived mitochondrial mutant through activation of stress response pathways.
Article in BMC biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 125 citations in OpenAlex.
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- InsP3R signaling and actomyosin-dependent mitochondrial dynamics play essential roles in mitochondrial stress-induced longevity.Nature communications · 2026Article
- Intervening in aging and related diseases with gene therapy techniques.Cell reports. Medicine · 2026Review
- Multiple Molecular Pathways to Longevity: Opposing Gene Expression Programs Define Distinct Aging Strategies.bioRxiv : the preprint server for biology · 2026Article
- A Forward Genetic Screen inbioRxiv : the preprint server for biology · 2026Article
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- MAK-2 Kinase Is Required for Extended Longevity and Enhanced Stress Resistance Resulting From Mild Impairment of Mitochondrial Function in isp-1 Mutants.Aging cell · 2026Article
- Targeting Mitochondrial Stress Responses: Terbinafine and Miglustat as Novel Lifespan and Healthspan Modulators.Aging cell · 2026Article
- Immune regulators PALS-25 and PALS-22 localize to mitochondria and regulate mitochondrial fragmentation iniScience · 2026Article
- Decoding the gut microbiota-mitochondrial-inflammasome axis in cardiovascular disease.Molecular and cellular biochemistry · 2026Review
- Mild Mitochondrial Impairment Activates Overlapping Longevity Pathways Converging on the Flavin-Containing Monooxygenase FMO-2.bioRxiv : the preprint server for biology · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- High confidence HIF-1 target genes for quantifying the activation of the HIF-1-mediated hypoxia response.microPublication biology · 2026Article
- Mild mitochondrial impairment activates overlapping longevity pathways converging on the flavin-containing monooxygenase FMO-2.Frontiers in aging · 2026Article
- Iron-deplete diet enhances Caenorhabditis elegans lifespan via oxidative stress response pathways.The EMBO journal · 2025Article
- Involvement of mitochondrial unfolded protein response and activating transcription factor 4 in the mitochondrial damage pathway of BEAS-2B cells induced by cigarette smoke extracts.Journal of thoracic disease · 2025Article
- Human gut Bifidobacteria strains regulate host longevity via shared and divergent mechanisms inbioRxiv : the preprint server for biology · 2025Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe mitochondrial unfolded protein response (mitoUPR) is a stress response pathway activated by disruption of proteostasis in the mitochondria. This pathway has been proposed to influence lifespan, with studies suggesting that mitoUPR activation has complex effects on longevity.
resultsHere, we examined the contribution of the mitoUPR to the survival and lifespan of three long-lived mitochondrial mutants in Caenorhabditis elegans by modulating the levels of ATFS-1, the central transcription factor that mediates the mitoUPR. We found that clk-1, isp-1, and nuo-6 worms all exhibit an ATFS-1-dependent activation of the mitoUPR. While loss of atfs-1 during adulthood does not affect lifespan in any of these strains, absence of atfs-1 during development prevents clk-1 and isp-1 worms from reaching adulthood and reduces the lifespan of nuo-6 mutants. Examining the mechanism by which deletion of atfs-1 reverts nuo-6 lifespan to wild-type, we find that many of the transcriptional changes present in nuo-6 worms are mediated by ATFS-1. Genes exhibiting an ATFS-1-dependent upregulation in nuo-6 worms are enriched for transcripts that function in stress response and metabolism. Consistent, with this finding, loss of atfs-1 abolishes the enhanced stress resistance observed in nuo-6 mutants and prevents upregulation of multiple stress response pathways including the HIF-1-mediated hypoxia response, SKN-1-mediated oxidative stress response and DAF-16-mediated stress response.
conclusionsOur results suggest that in the long-lived mitochondrial mutant nuo-6 activation of the mitoUPR causes atfs-1-dependent changes in the expression of genes involved in stress response and metabolism, which contributes to the extended longevity observed in this mutant. This work demonstrates that the mitoUPR can modulate multiple stress response pathways and suggests that it is crucial for the development and lifespan of long-lived mitochondrial mutants.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.