ArticlePLoS genetics2021
Nuclear receptors NHR-49 and NHR-79 promote peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- A somatic checkpoint through NHR-49/HNF4α governs reproductive investment and longevity in C. elegans.Nature communications · 2026Article
- A conserved ER protein prevents lipotoxicity by stimulating the key enzyme in glycerolipid synthesis.Nature communications · 2026Article
- Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3.Acta pharmaceutica Sinica. B · 2026Article
- Silencing lipid catabolism determines longevity in response to fasting.Nature communications · 2026Article
- A new set of combinatorial dimeric codes for nuclear hormone receptor-target gene specificity.Nucleic acids research · 2026Article
- ALH Inhibition as a Molecular Initiating Event in the Adverse Outcome Pathway of Benomyl Toxicity inInternational journal of molecular sciences · 2025Article
- Nuclear Hormone Receptor NHR-49/HNF4α Couples Fertility Regulation to Resource Allocation and Longevity inbioRxiv : the preprint server for biology · 2025Article
- Article
- Matrine Inhibits High-Glucose-Diet-Induced Fat Accumulation and Aβ-Mediated Lipid Metabolic Disorder via AAK-2/NHR-49 Pathway inInternational journal of molecular sciences · 2025Article
- Peripheral peroxisomal β-oxidation engages neuronal serotonin signaling to drive stress-induced aversive memory in C. elegans.Cell reports · 2024Article
- ESYT1 tethers the ER to mitochondria and is required for mitochondrial lipid and calcium homeostasis.Life science alliance · 2024Article
- Systems-level transcriptional regulation of Caenorhabditis elegans metabolism.Molecular systems biology · 2023Article
- Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids.Nature cell biology · 2023Article
- Nuclear hormone receptor NHR-49 is an essential regulator of stress resilience and healthy aging inFrontiers in physiology · 2023Review
- Endocrine pheromones couple fat rationing to dauer diapause through HNF4α nuclear receptors.Science China. Life sciences · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The intracellular level of fatty aldehydes is tightly regulated by aldehyde dehydrogenases to minimize the formation of toxic lipid and protein adducts. Importantly, the dysregulation of aldehyde dehydrogenases has been implicated in neurologic disorder and cancer in humans. However, cellular responses to unresolved, elevated fatty aldehyde levels are poorly understood. Here, we report that ALH-4 is a C. elegans aldehyde dehydrogenase that specifically associates with the endoplasmic reticulum, mitochondria and peroxisomes. Based on lipidomic and imaging analysis, we show that the loss of ALH-4 increases fatty aldehyde levels and reduces fat storage. ALH-4 deficiency in the intestine, cell-nonautonomously induces NHR-49/NHR-79-dependent hypodermal peroxisome proliferation. This is accompanied by the upregulation of catalases and fatty acid catabolic enzymes, as indicated by RNA sequencing. Such a response is required to counteract ALH-4 deficiency since alh-4; nhr-49 double mutant animals are sterile. Our work reveals unexpected inter-tissue communication of fatty aldehyde levels and suggests pharmacological modulation of peroxisome proliferation as a therapeutic strategy to tackle pathology related to excess fatty aldehydes.
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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 Socratic graph.