Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes

Jin Young Baek, Sujin Park, Jiyoung Park, Ji Yong Jang, Su Bin Wang, Sin Ri Kim, Hyun Ae Woo, Kyung Min Lim, Tong Shin Chang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

UVB light induces generation of reactive oxygen species, ultimately leading to skin cell damage. Mitochondria are a major source of reactive oxygen species in UVB-irradiated skin cells, with increased levels of mitochondrial reactive oxygen species having been implicated in keratinocyte apoptosis. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-removing enzyme in the mitochondria of most cell types. Here, the protective role of PrxIII against UVB-induced apoptosis of epidermal keratinocytes was investigated. Mitochondrial H2O2 levels were differentiated from other types of ROS using mitochondria-specific fluorescent H2O2 indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII–/–) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H2O2 compared with PrxIII-expressing controls. Keratinocytes lacking PrxIII were subsequently sensitized to apoptosis through mitochondrial membrane potential loss, cardiolipin oxidation, cytochrome c release, and caspase activation. Increased UVB-induced epidermal tissue damage in PrxIII–/– mice was attributable to increased caspase-dependent keratinocyte apoptosis. Our findings show that mitochondrial H2O2 is a key mediator in UVB-induced apoptosis of keratinocytes and that PrxIII plays a critical role in protecting epidermal keratinocytes against UVB-induced apoptosis through eliminating mitochondrial H2O2. These findings support the concept that reinforcing mitochondrial PrxIII defenses may help prevent UVB-induced skin damage such as inflammation, sunburn, and photoaging.

Original languageEnglish
Pages (from-to)1333-1342
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number6
DOIs
StatePublished - Jun 2017

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