title: Quercetin induces mitochondrial biogenesis through activation of HO-1 in HepG2 cells.
abstract: The regeneration of mitochondria by regulated biogenesis plays an important homeostatic role in cells and tissues and furthermore may provide an adaptive mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells. Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO-1/CO system. This study focused on the mechanism by which the natural antioxidant quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that quercetin treatment induced expression of mitochondrial biogenesis activators (PGC-1 α , NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory effects of quercetin on mitochondrial biogenesis could be recapitulated in vivo in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti-inflammatory effect in the liver of mice treated with LPS and prevented impairment of mitochondrial biogenesis by LPS in vivo. These salutary effects of quercetin in vivo were also antagonized by SnPP. Thus, our results suggest that quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system in vitro and in vivo. The beneficial effects of quercetin may provide a therapeutic basis in inflammatory diseases and sepsis.
authors.affiliation: School of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea ; Chitwan Medical College, Bharatpur-10, Chitwan, Nepal.
authors.forename: Nabin
authors.initials: N
authors.lastname: Rayamajhi
authors.forename: Seul-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Hiroe
authors.initials: H
authors.lastname: Go
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Joe
authors.forename: Zak
authors.initials: Z
authors.lastname: Callaway
authors.forename: Jae-Gu
authors.initials: JG
authors.lastname: Kang
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Ryter
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D063269:Mitochondrial Turnover / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D024101:Mitochondrial Proteins; D002248:Carbon Monoxide; D011794:Quercetin; D051547:Heme Oxygenase-1