title: Impact of hyperpigmentation on superoxide flux and melanoma cell metabolism at mitochondrial complex II.
abstract: Melanogenesis is a highly conserved process of cytophotoprotection from UV radiation present in many species. Although both mitochondrial function and UV radiation insults are well-documented promoters of increased cellular stress, their individual molecular relationships with skin pigmentation have not been clearly resolved. This study provides evidence for a direct relationship between cellular melanin content, superoxide flux, and mitochondrial function at complex II. Direct and significant correlation between increased pigmentation and complex II turnover was observed in genetically different melanoma cell lines of varied basal pigmentation states (P < 0.01). The same trend was also observed when comparing genetically identical cell cultures with increasing levels of induced pigmentation (P < 0.005). The observation of increased steady-state levels of the catalytic complex II succinate dehydrogenase subunit A alongside hyperpigmentation suggested coregulation of activity and pigment production (P < 0.01). The study also presents novel evidence for a relationship between hyperpigmentation and increased superoxide-generating capacity at complex II. By amperometrically monitoring superoxide flux from differently pigmented FM55 melanocytes and their isolated mitochondria, a dynamic and responsive relationship between pigmentation, complex II function, and intracellular superoxide generation was observed (P < 0.005). The data support hyperpigmentation as a protective antioxidant mechanism in response to complex II-mediated reactive oxygen species generation.
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Sarah Jayne
authors.initials: SJ
authors.lastname: Boulton
authors.affiliation: Dermatological Sciences, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom mark.birch-machin@ncl.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birch-Machin
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D045744:Cell Line, Tumor; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017495:Hyperpigmentation / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D021122:Protein Subunits; D012878:Skin Neoplasms / Q000378:metabolism*; D012880:Skin Pigmentation / Q000502:physiology; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D008543:Melanins; D009574:Nitro Compounds; D011422:Propionates; D021122:Protein Subunits; D013481:Superoxides; D013804:Thenoyltrifluoroacetone; D042963:Electron Transport Complex II; C511268:SDHA protein, human; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid
keywords: bioenergetics; cytoprotection; melanin; skin; succinate dehydrogenase