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A chemical screen to identify inducers of the mitochondrial unfolded protein response in C. elegans

Artikel i vetenskaplig tidskrift
Författare Manish Rauthan
Marc Pilon
Publicerad i WORM
Volym 4
Nummer/häfte 4
Sidor e1096490
ISSN 2162-4054
Publiceringsår 2015
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor e1096490
Språk en
Länkar dx.doi.org/10.1080/21624054.2015.10...
Ämnesord C elegans, chemical screen, ethidium bromide, mitochondrial unfolded protein response, methacycline hydrochloride, statin
Ämneskategorier Biologiska vetenskaper

Sammanfattning

We previously showed that inhibition of the mevalonate pathway in C. elegans causes inhibition of protein prenylation, developmental arrest and lethality. We also showed that constitutive activation of the mitochondrial unfolded protein response, UPRmt, is an effective way for C. elegans to become resistant to the negative effects of mevalonate pathway inhibition. This was an important finding since statins, a drug class prescribed to lower cholesterol levels in patients, act by inhibiting the mevalonate pathway, and it is therefore possible that some of their undesirable side effects could be alleviated by activating the UPRmt. Here, we screened a chemical library and identified 4 compounds that specifically activated the UPRmt. One of these compounds, methacycline hydrochloride (a tetracycline antibiotic) also protected C. elegans and mammalian cells from statin toxicity. Methacycline hydrochloride and ethidium bromide, a known UPRmt activator, were also tested in mice: only ethidium bromide significantly activate the UPRmt in skeletal muscles.

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