Development of a novel in vitro model to study the modulatory role of the respiratory complex I in macrophage effector functions

• Published in: PloS one Vol. 18; no. 9; p. e0291442
• Main Authors: Serrano-Lorenzo, Pablo, Gobelli, Dino, Garrido-Moraga, Rocío, Esteban-Amo, María J, López-López, José R, Orduña, Antonio, de la Fuente, Miguel A, Martín, Miguel A, Simarro, María
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 19-09-2023; Public Library of Science (PLoS)
• Subjects: Animal experimentation; Bacteria; Biology and Life Sciences; Cell lines; Cloning; CRISPR; Cytokines; Electron transfer; Electron transport; Electron transport chain; Enzymes; Ethylenediaminetetraacetic acid; Evaluation; Genomes; Genomics; Gram-negative bacteria; Health aspects; Homogenization; Inflammation; Lipopolysaccharides; Macrophages; Medicine and Health Sciences; Membranes; Mitochondria; Mutation hot spots; NDUFS4 gene; Plasmids; Proteins; Research and Analysis Methods; Respiration; Scientific equipment and supplies industry; Sucrose; Supernumerary; Spain; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0291442

Increasing evidence demonstrate that the electron transfer chain plays a critical role in controlling the effector functions of macrophages. In this work, we have generated a Ndufs4-/- murine macrophage cell lines. The Ndufs4 gene, which encodes a supernumerary subunit of complex I, is a mutational hotspot in Leigh syndrome patients. Ndufs4-/- macrophages showed decreased complex I activity, altered complex I assembly, and lower levels of maximal respiration and ATP production. These mitochondrial respiration alterations were associated with a shift towards a pro-inflammatory cytokine profile after lipopolysaccharide challenge and improved ability to phagocytose Gram-negative bacteria.