ArticleDevelopmental cell2011
A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila.
Article in Developmental cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 95 citations in OpenAlex.
- The Diverse Roles of the MEF2 Transcription Factor Family in Tumor Progression and Emerging Therapeutic Opportunities.Biomedicines · 2026Review
- The other giant: functional significance and divergence of Type I MADS-box genes in the evolution of land plants.Journal of experimental botany · 2026Review
- Angiotensin-Converting Enzyme Inhibitors and Metabolic Aging: A Drosophila Perspective.Biomolecules · 2025Review
- Impacts of mitochondrial dysfunction on axonal microtubule bundles as a potential mechanism of neurodegeneration.Frontiers in neuroscience · 2025Review
- Targeted Bmal1 restoration in muscle prolongs lifespan with systemic health effects in aging model.JCI insight · 2024Article
- Systemic Effects of Photoactivated 5,10,15,20-tetrakis(Biotech (Basel (Switzerland)) · 2024Article
- Host JAK-STAT activity is a target of parasitoid wasp virulence strategies.PLoS pathogens · 2024Article
- Updated Phylogeny and Protein Structure Predictions Revise the Hypothesis on the Origin of MADS-box Transcription Factors in Land Plants.Molecular biology and evolution · 2023Article
- Optimization of ultrasound-assisted extraction method for phytochemical compounds and antioxidant activities of sour jujube extracts.Food science & nutrition · 2022Article
- Chromosome-level genome assembly of Bactrocera dorsalis reveals its adaptation and invasion mechanisms.Communications biology · 2022Article
- Drosophila p38 MAPK interacts with BAG-3/starvin to regulate age-dependent protein homeostasis.Aging cell · 2021Article
- Functional conservation in genes and pathways linking ageing and immunity.Immunity & ageing : I & A · 2021Review
- Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src ineLife · 2021Article
- The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging.Oxidative medicine and cellular longevity · 2021Review
- Proteostasis-associated aging: lessons from a Drosophila model.Genes & genomics · 2021Review
- Mitochondrial Redox Signaling Is Critical to the Normal Functioning of the Neuronal System.Frontiers in cell and developmental biology · 2021Article
- Hypersensitivity of Vps33B mutant flies to non-pathogenic infections is dictated by aberrant activation of p38b MAP kinase.Traffic (Copenhagen, Denmark) · 2020Article
- Evolutionarily conserved transcription factors drive the oxidative stress response inThe Journal of experimental biology · 2020Article
- Upregulated TNF/Eiger signaling mediates stem cell recovery and tissue homeostasis during nutrient resupply in Drosophila testis.Scientific reports · 2020Article
- The Phosphatase CSW Controls Life Span by Insulin Signaling and Metabolism Throughout Adult Life inFrontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Molecular mechanisms that concordantly regulate stress, life span, and aging remain incompletely understood. Here, we demonstrate that in Drosophila, a p38 MAP kinase (p38K)/Mef2/MnSOD pathway is a coregulator of stress and life span. Hence, overexpression of p38K extends life span in a MnSOD-dependent manner, whereas inhibition of p38K causes early lethality and precipitates age-related motor dysfunction and stress sensitivity, that is rescued through muscle-restricted (but not neuronal) add-back of p38K. Additionally, mutations in p38K are associated with increased protein carbonylation and Nrf2-dependent transcription, while adversely affecting metabolic response to hypoxia. Mechanistically, p38K modulates expression of the mitochondrial MnSOD enzyme through the transcription factor Mef2, and predictably, perturbations in MnSOD modify p38K-dependent phenotypes. Thus, our results uncover a muscle-restricted p38K-Mef2-MnSOD signaling module that influences life span and stress, distinct from the insulin/JNK/FOXO pathway. We propose that potentiating p38K might be instrumental in restoring the mitochondrial detoxification machinery and combating stress-induced aging.
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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.