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

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.

Automated summary

Increasing evidence shows that the electron transfer chain is crucial in controlling macrophages' effector functions. This study generated Ndufs4-/- mouse macrophage cell lines, which exhibit decreased complex I activity, altered complex I assembly, and reduced levels of maximal respiration and ATP production. These mitochondrial respiration alterations are associated with a pro-inflammatory cytokine profile response and enhanced phagocytosis of Gram-negative bacteria.