Histone deacetylase 7 mediates lipopolysaccharide-inducible mitochondrial fission in macrophages
Year: 2025
Type: article
Abstract: Histone deacetylase 7 (HDAC7) drives several immunometabolism-related processes in macrophages including lipopolysaccharide (LPS)-inducible glycolysis and inflammatory mediator production. Using an advanced biotin ligase TurboID system in human macrophages, we report 104 candidate HDAC7 interaction partners that might contribute to its immunometabolic functions. One such protein is the mitochondrial fission-promoting GTPase dynamin-related protein 1 (DRP1, also known as DNM1L), which associates with HDAC7 in cells. Using gain- and loss-of-function genetic approaches, we show that HDAC7 promotes LPS-inducible mitochondrial fission in macrophages, as well as DRP1-dependent metabolic and inflammatory responses. HDAC7 enzymatic activity was dispensable for LPS-inducible fission, as previously reported for LPS-inducible glycolysis. However, a pharmacological inhibitor of HDAC7 attenuated fission in primary human and mouse macrophages, implicating its acetyl-lysine docking function in this response. HDAC7 thus drives inducible mitochondrial fission in macrophages. Small molecules targeting the acetyl-lysine docking function of HDAC7 might have applications in preventing pathological processes driven by dysregulated mitochondrial fission.
Source: Journal of Cell Science
DOI: 10.1242/jcs.264376
Authors: Rishika Abrol, Syeda Farhana Afroz, James E. B. Curson, Karoline D. Raven, Kaustav Das Gupta, Kimberley S. Gunther, Alun Jones, Robert C. Reid, Zherui Xiong, Jennifer H. Gunter, Jessica A. Engel, Christian R. Engwerda, Antje Blumenthal, David P. Fairlie, Robert G. Parton, Steven Zuryn, Ronan Kapetanovic, Divya Ramnath, Matthew J. Sweet
Institutions: The University of Queensland, Institute for Molecular Bioscience, University of California, Los Angeles, The Lundquist Institute, Los Angeles Medical Center, Harbor–UCLA Medical Center, Translational Research Institute, Queensland University of Technology, Australian Prostate Centre, QIMR Berghofer Medical Research Institute, ARC Centre of Excellence for Innovations in Peptide and Protein Science, Centre for Microscopy and Microanalysis, Université de Tours, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement, Infectiologie et santé publique
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: Mitochondria as sensors of environmental threats, Molecular drivers of metabolic reprogramming in Mycobacterium tuberculosis infection, Reprogramming innate immunity to combat inflammatory and infectious diseases, Modulating protein-protein interactions in disease, G4209227257, G5572172683, New Frontiers in Innate Immunity, Defining molecular links between immune cell metabolism and inflammation
OpenAlex ID: W4413898656