Figure 4.

Overview of the processes affecting oxygen consumption in M(2-signals) macrophages. The main source of oxygen consumption in macrophages (as in all cells) is the terminal electron (e⁻) donor at ETC complex IV (heme a3-Cu_B center). Upon 2-signals activation (e.g., IFNγ + LPS or IFNγ + Pam3CSK4), the macrophages express iNOS, leading to production of NO^●. NO^● reversibly inhibits the O₂ attachment to complex IV, causing even higher electron leak from the ETC. These electrons can reduce O₂ to O₂^●−, which then can bind with NO^● and produce ONOO⁻. Alternatively, NO^● can react with O₂ and produce NO₂¯ and/or NO₃¯. Inhibitors [1400 W (iNOS)] and scavengers [PTiO/carboxyPTiO (NO^●), MnTmPyP (O₂^●−)] on various levels (indicated with red lines) hamper the production of these free radicals, leading to the partial recovery of respiration.