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

by Pablo Serrano-Lorenzo, Dino Gobelli, Rocío Garrido-Moraga, María J. Esteban-Amo, José R. López-López, Antonio Orduña, Miguel A. de la Fuente, Miguel A. Martín, María Simarro

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.