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Mitochondrial metabolic reprograming via BRAF inhibition ameliorates senescence

Title
Mitochondrial metabolic reprograming via BRAF inhibition ameliorates senescence
Authors
Kim, Jae WonKuk, Myeong UkChoy, Hyon E.Park, Sang ChulPark, Joon Tae
Issue Date
2019-10
Citation
Experimental Gerontology, 126
Type
Article
Article Type
Article
Author Keywords
BRAFMetabolic reprogrammingMitochondrial functionSB590885Senescence
Keywords
LIPOFUSCINACCUMULATIONAUTOPHAGYQUANTIFICATIONALLEVIATIONDYSFUNCTIONPATHWAYSKINASETARGETROCK
ISSN
0531-5565
Abstract
Senescence is defined as irreversible cell cycle arrest and constitutes a major driving force in diseases related to aging or premature aging. Recent studies indicate that activation of the serine/threonine protein kinase B-raf (BRAF) plays important roles in oncogene-induced senescence. However, it remains elusive whether BRAF inhibition might be effective for abrogating senescence. In this study, we assessed several BRAF inhibitors to identify compounds that ameliorate senescence and revealed SB590885 as an effective agent. Senescence-ameliorating effect upon BRAF inhibition was evident from the observation that SB590885 treatment increased cellular proliferation but diminished senescent phenotypes. Moreover, BRAF inhibition induced the mitochondrial functional recovery along with the metabolic reprogramming, which comprises two salient features that are altered in senescent cells. Furthermore, mitochondrial metabolic reprogramming via BRAF inhibition was a prerequisite for senescence amelioration. Taken together, our data revealed a novel mechanism in which senescence amelioration is mediated by mitochondrial metabolic reprogramming upon BRAF inhibition. © 2019 Elsevier Inc.
URI
http://hdl.handle.net/20.500.11750/10939
DOI
10.1016/j.exger.2019.110691
Publisher
Elsevier Inc.
Files:
There are no files associated with this item.
Collection:
ETC1. Journal Articles


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