Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission
| Autor: | William L. Berry, Gary B. O'Mealey, Scott M. Plafker |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
0301 basic medicine
Dynamins Fission NF-E2-Related Factor 2 Clinical Biochemistry Apoptosis Retinal Pigment Epithelium Drp1 Mitochondrion Biology medicine.disease_cause Biochemistry Mitochondrial Dynamics Antioxidants Nrf2 03 medical and health sciences chemistry.chemical_compound Isothiocyanates medicine Staurosporine Humans Fusion lcsh:QH301-705.5 lcsh:R5-920 Kelch-Like ECH-Associated Protein 1 Organic Chemistry respiratory system KEAP1 Cytoprotection Cell biology Mitochondria Oxidative Stress 030104 developmental biology mitochondrial fusion chemistry lcsh:Biology (General) Sulfoxides Mitochondrial fission lcsh:Medicine (General) Carboxylic Ester Hydrolases Sulforaphane Oxidative stress medicine.drug Signal Transduction Research Paper |
| Zdroj: | Redox Biology, Vol 11, Iss, Pp 103-110 (2017) Redox Biology |
| ISSN: | 2213-2317 |
| DOI: | 10.1016/j.redox.2016.11.007 |
| Popis: | The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials. Keywords: Sulforaphane, Nrf2, Drp1, Mitochondria, Fission, Fusion, Apoptosis |
| Databáze: | OpenAIRE |
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