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

PLoS One. 2023 Sep 19;18(9):e0291442. doi: 10.1371/journal.pone.0291442. eCollection 2023.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Electron Transport Complex I* / genetics
  • Humans
  • Leigh Disease*
  • Macrophages
  • Mice
  • Phagocytosis

Substances

  • Electron Transport Complex I
  • Ndufs4 protein, mouse

Grants and funding

Ministerio de Ciencia e Innovación, PID2020-118517RB-I00 Consejería de Educación, Junta de Castilla y León, VA172P20 Consejería de Sanidad, Junta de Castilla y León, GRS 2201/A/2020 Instituto de Salud Carlos III, PI21/00381 Junta de Castilla y León, CCVC8485.