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Redox Biol. 2017 Apr;11:103-110. doi: 10.1016/j.redox.2016.11.007. Epub 2016 Nov 21.

Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission.

Author information

1
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States.
2
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
3
Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States. Electronic address: plafkers@omrf.org.

Abstract

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:

Apoptosis; Drp1; Fission; Fusion; Mitochondria; Nrf2; Sulforaphane

PMID:
27889639
PMCID:
PMC5126150
DOI:
10.1016/j.redox.2016.11.007
[Indexed for MEDLINE]
Free PMC Article

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