Fig. 2

The mitochondrial and endoplasmic reticulum (ER) stress induced by 4-hexylresorcinol (4HR). The protein bound to 4HR changes its conformation. It is recognized by GRP78 and GRP78 tagged protein is transported to ER. It increases phosphorylation of PERK and eIF2, sequentially. It suppresses general gene translation and induces ATF4 induced cellular apoptosis. By the way, 4HR suppresses mitochondrial respiration and ATP synthesis. Mitochondrial membrane potential (MMP) and nicotinamide adenine dinucleotide hydrate (NADH) are increased sirtuin (SIRT) expression and its activity. SIRT can suppress eIF2 activity and this alleviates ER-induced apoptotic stress. Mitochondrial stress activates many kinases and Sp1 phosphorylation. Decreased histone deacetylase activity by 4HR administration increases acetylation of histone 3 (H3). Sp1 phosphorylation and hyper-acetylation of H3 increases transforming growth factor-β1 (TGF-β1) transcription activity (reproduced from author’s own work [13])