ArticlePLoS genetics2016
DLK-1, SEK-3 and PMK-3 Are Required for the Life Extension Induced by Mitochondrial Bioenergetic Disruption in C. elegans.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Box C/D snoRNPs and MDT-15/MED15 regulate mitochondrial surveillance and mitophagy via fatty acid metabolism.GeroScience · 2026Article
- Mitochondrial stress activates ELT-2-dependent lysosomal proteostasis to extend lifespan inScience advances · 2026Article
- Mitochondrial redox homeostasis links organellar stress surveillance to germline and somatic integrity in Caenorhabditis elegans.Redox biology · 2026Article
- 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
- The hippo pathway: a molecular bridge between environmental cues and pace of life.BMC ecology and evolution · 2025Review
- Mitochondrial p38 Mitogen-Activated Protein Kinase: Insights into Its Regulation of and Role in LONP1-Deficient Nematodes.International journal of molecular sciences · 2023Article
- Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity.Aging and disease · 2023Review
- Examining Sporadic Cancer Mutations Uncovers a Set of Genes Involved in Mitochondrial Maintenance.Genes · 2023Article
- Endosomal trafficking protein TBC-2 is required for the longevity of long-lived mitochondrial mutants.Frontiers in aging · 2023Article
- Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress.Open biology · 2023Article
- Mitochondrial succinate dehydrogenase function is essential for sperm motility and male fertility.iScience · 2022Article
- Mitochondria-originated redox signalling regulates KLF-1 to promote longevity in Caenorhabditis elegans.Redox biology · 2022Article
- The emergent role of mitochondrial surveillance in cellular health.Aging cell · 2022Review
- Forward genetic screening identifies novel roles for N-terminal acetyltransferase C and histone deacetylase in C. elegans development.Scientific reports · 2022Article
- Article
- Mitochondria-derived peptides in aging and healthspan.The Journal of clinical investigation · 2022Review
- A tRNA processing enzyme is a key regulator of the mitochondrial unfolded protein response.eLife · 2022Article
- Box C/D small nucleolar ribonucleoproteins regulate mitochondrial surveillance and innate immunity.PLoS genetics · 2022Article
- The Expression and Function of Tubulin Isotypes inFrontiers in cell and developmental biology · 2022Review
- Mild mitochondrial impairment enhances innate immunity and longevity through ATFS-1 and p38 signaling.EMBO reports · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Mitochondrial dysfunction underlies numerous age-related pathologies. In an effort to uncover how the detrimental effects of mitochondrial dysfunction might be alleviated, we examined how the nematode C. elegans not only adapts to disruption of the mitochondrial electron transport chain, but in many instances responds with extended lifespan. Studies have shown various retrograde responses are activated in these animals, including the well-studied ATFS-1-dependent mitochondrial unfolded protein response (UPRmt). Such processes fall under the greater rubric of cellular surveillance mechanisms. Here we identify a novel p38 signaling cascade that is required to extend life when the mitochondrial electron transport chain is disrupted in worms, and which is blocked by disruption of the Mitochondrial-associated Degradation (MAD) pathway. This novel cascade is defined by DLK-1 (MAP3K), SEK-3 (MAP2K), PMK-3 (MAPK) and the reporter gene Ptbb-6::GFP. Inhibition of known mitochondrial retrograde responses does not alter induction of Ptbb-6::GFP, instead induction of this reporter often occurs in counterpoint to activation of SKN-1, which we show is under the control of ATFS-1. In those mitochondrial bioenergetic mutants which activate Ptbb-6::GFP, we find that dlk-1, sek-3 and pmk-3 are all required for their life extension.
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Registered trials
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.