title: Trifloxystrobin-induced mitophagy through mitochondrial damage in human skin keratinocytes.
abstract: Trifloxystrobin is a strobilurin class fungicide, the mode of action of which is to block the mitochondrial electron transport chain and inhibit energy production in fungi. Although adverse effects have been reported by occupational or environmental exposure of fungicides, the pathophysiological mechanism in human cells remains poorly understood. In the present study, we investigated the impact of trifloxystrobin on exposed skin at the cellular organelle level using HaCaT, the human skin keratinocyte cell line. Cells were treated with trifloxystrobin for 48 hr and trifloxystrobin showed detrimental effects on mitochondria evidenced by altered mitochondrial membrane potential and morphology. To identify autophagic degradation of the damaged mitochondria, confocal imaging and Western blotting were performed. Trifloxystrobin induced autophagy-related proteins in HaCaT cells. The mitochondrial reactive oxygen species scavenger mitoTEMPO was applied to further explore the mechanism of trifloxystrobin-mediated mitophagy in human skin cells. PINK1 and Parkin were overexpressed by trifloxystrobin, and mitoTEMPO alleviated the effects on mitophagy induction. Taken together, our findings indicated that mitochondrial damage and mitophagy may play a role in trifloxystrobin-induced toxicity in human keratinocytes and this could be suggested as a mechanism of cutaneous diseases developed by exposure.
authors.affiliation: Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Korea.
authors.forename: Yoonjeong
authors.initials: Y
authors.lastname: Jang
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Paik
authors.forename: Jun Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
mesh_terms: D000085:Acetates / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000633:toxicity*; D006801:Humans; D007097:Imines / Q000633:toxicity*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008689:Methacrylates / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D063306:Mitophagy / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D000073739:Strobilurins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D015854:Up-Regulation; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000085:Acetates; D016166:Free Radical Scavengers; D005659:Fungicides, Industrial; D007097:Imines; D008689:Methacrylates; D009943:Organophosphorus Compounds; D010880:Piperidines; D011494:Protein Kinases; D000073739:Strobilurins; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C555916:MitoTEMPO; C111567:parkin protein; C467051:trifloxystrobin