Abstract:
:Accumulating studies have argued that the mitochondrial unfolded protein response (UPRmt) is a mitochondrial stress response that promotes longevity in model organisms. In the present study, we screened an off-patent drug library to identify compounds that activate UPRmt using a mitochondrial chaperone hsp-6::GFP reporter system in Caenorhabditis elegans. Metolazone, a diuretic primarily used to treat congestive heart failure and high blood pressure, was identified as a prominent hit as it upregulated hsp-6::GFP and not the endoplasmic reticulum chaperone hsp-4::GFP. Furthermore, metolazone specifically induced the expression of mitochondrial chaperones in the HeLa cell line. Metolazone also extended the lifespan of worms in a atfs-1 and ubl-5-dependent manner. Notably, metolazone failed to increase lifespan in worms with knocked-down nkcc-1. These results suggested that metolazone activates the UPRmt across species and prolongs the lifespan of C. elegans.
journal_name
Biogerontologyjournal_title
Biogerontologyauthors
Ito A,Zhao Q,Tanaka Y,Yasui M,Katayama R,Sun S,Tanimoto Y,Nishikawa Y,Kage-Nakadai Edoi
10.1007/s10522-020-09907-6subject
Has Abstractpub_date
2021-02-01 00:00:00pages
119-131issue
1eissn
1389-5729issn
1573-6768pii
10.1007/s10522-020-09907-6journal_volume
22pub_type
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