ArticleScientific reports2017
Molecular Basis of ABHD5 Lipolysis Activation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- TRPA1 deficiency alters brown adipose tissue proteome and thermogenic gene expression during cold exposure in mice.Biochemistry and biophysics reports · 2026Article
- Current Research Progress on ABHD5 in Cancers.Cancers · 2026Review
- Patatin-domain-containing (phospho)lipases under control: Mammalian co-regulators and pathogenic activation mechanisms.FEBS open bio · 2026Review
- Defective targeting of PNPLA1 to lipid droplets causes ichthyosis in ABHD5-syndromic epidermal differentiation disorder.Journal of lipid research · 2025Article
- Unraveling the Molecular Mechanisms of ABHD5 Membrane Targeting.bioRxiv : the preprint server for biology · 2025Article
- Metabolic reprogramming of interleukin-17-producing γδ T cells promotes ACC1-mediated de novo lipogenesis under psoriatic conditions.Nature metabolism · 2025Article
- Using chanarin-dorfman syndrome patient fibroblasts to explore disease mechanisms and new treatment avenues.Orphanet journal of rare diseases · 2025Article
- Lipid droplet targeting of ABHD5 and PNPLA3 I148M is required to promote liver steatosis.bioRxiv : the preprint server for biology · 2024Article
- Unmasking crucial residues in adipose triglyceride lipase for coactivation with comparative gene identification-58.Journal of lipid research · 2024Article
- A FRET sensor for the real-time detection of long chain acyl-CoAs and synthetic ABHD5 ligands.Cell reports methods · 2023Article
- Review
- Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.Science (New York, N.Y.) · 2022Article
- Article
- Structural and functional insights into ABHD5, a ligand-regulated lipase co-activator.Scientific reports · 2022Article
- Molecular Modeling of ABHD5 Structure and Ligand Recognition.Frontiers in molecular biosciences · 2022Article
- Adipose Triglyceride Lipase in Hepatic Physiology and Pathophysiology.Biomolecules · 2021Review
- Lipolysis: cellular mechanisms for lipid mobilization from fat stores.Nature metabolism · 2021Review
- Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression.Journal of experimental & clinical cancer research : CR · 2020Article
- The ATGL lipase cooperates with ABHD5 to mobilize lipids for hepatitis C virus assembly.PLoS pathogens · 2020Article
- The Lipolysome-A Highly Complex and Dynamic Protein Network Orchestrating Cytoplasmic Triacylglycerol Degradation.Metabolites · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alpha-beta hydrolase domain-containing 5 (ABHD5), the defective gene in human Chanarin-Dorfman syndrome, is a highly conserved regulator of adipose triglyceride lipase (ATGL)-mediated lipolysis that plays important roles in metabolism, tumor progression, viral replication, and skin barrier formation. The structural determinants of ABHD5 lipolysis activation, however, are unknown. We performed comparative evolutionary analysis and structural modeling of ABHD5 and ABHD4, a functionally distinct paralog that diverged from ABHD5 ~500 million years ago, to identify determinants of ABHD5 lipolysis activation. Two highly conserved ABHD5 amino acids (R299 and G328) enabled ABHD4 (ABHD4 N303R/S332G) to activate ATGL in Cos7 cells, brown adipocytes, and artificial lipid droplets. The corresponding ABHD5 mutations (ABHD5 R299N and ABHD5 G328S) selectively disrupted lipolysis without affecting ATGL lipid droplet translocation or ABHD5 interactions with perilipin proteins and ABHD5 ligands, demonstrating that ABHD5 lipase activation could be dissociated from its other functions. Structural modeling placed ABHD5 R299/G328 and R303/G332 from gain-of-function ABHD4 in close proximity on the ABHD protein surface, indicating they form part of a novel functional surface required for lipase activation. These data demonstrate distinct ABHD5 functional properties and provide new insights into the functional evolution of ABHD family members and the structural basis of lipase regulation.
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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.