Mitochondrial metabolism modulates gene expression in inflammatory and IL-4-stimulated macrophages. In inflammatory macrophages activated by microbial signals, mitochondrial fission dampens ETC efficiency and enhances aerobic glycolysis. Elevated ΔΨm leads to accumulation of mtROS and induction of Il1b gene and voltage-regulated genes (VRGs), all contribute to macrophage function. In IL-4-stimulated macrophages, mitochondrial fusion stimulates interactions between ETC complexes that are conducive to OXPHOS and FAO. PGE2 modulates the expression of genes encoding the malate-aspartate shuttle (MAS), leading to the decrease of ΔΨm, which increases the activity of ETS variant 1 (ETV1) to promote some IL-4-inducible gene expression. Degradation or turnover of mitochondria via mitophagy is regulated by BNIP3L/NIX receptor and AMPK and mTOR pathway.