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  Mitochondrial chaperonin HSP60 is the apoptosis-related target for myrtucommulone

Wiechmann, K., Müller, H., König, S., Wielsch, N., Svatoš, A., Jauch, J., et al. (2017). Mitochondrial chaperonin HSP60 is the apoptosis-related target for myrtucommulone. Cell Chemical Biology, 24(5), 614-623. doi:10.1016/j.chembiol.2017.04.008.

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 Creators:
Wiechmann, Katja, Author
Müller, Hans, Author
König, Stefanie, Author
Wielsch, Natalie1, Author           
Svatoš, Aleš1, Author           
Jauch, Johann, Author
Werz, Oliver, Author
Affiliations:
1Research Group Mass Spectrometry, MPI for Chemical Ecology, Max Planck Society, ou_421899              

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 Abstract: The acylphloroglucinol myrtucommulone A (MC) causes mitochondrial dysfunctions by direct interference leading to apoptosis in cancer cells, but the molecular targets involved are unknown. Here, we reveal the chaperonin heat-shock protein 60 (HSP60) as a molecular target of MC that seemingly modulates HSP60-mediated mitochondrial functions. Exploiting an unbiased, discriminative protein fishing approach usingMC as bait and mitochondrial lysates from leukemic HL-60 cells as target source identified HSP60 as an MC-binding protein. MC prevented HSP60-mediated reactivation of denatured malate dehydrogenase in a protein refolding assay. Interference of MC with HSP60 was accompanied by aggregation of two proteins in isolated mitochondria under heat shock that were identified as Lon protease-like protein (LONP) and leucine-rich PPR motif-containing protein (LRP130). Together, our results reveal HSP60 as a direct target of MC, proposing MC as a valuable tool for studying HSP60 biology and for evaluating its value as a target in related diseases, such as cancer.

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 Dates: 2017-04-062017-04-272017-05-18
 Publication Status: Issued
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 Identifiers: Other: MS186
DOI: 10.1016/j.chembiol.2017.04.008
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Title: Cell Chemical Biology
Source Genre: Journal
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Publ. Info: Cell Press
Pages: - Volume / Issue: 24 (5) Sequence Number: - Start / End Page: 614 - 623 Identifier: ISSN: 2451-9456
CoNE: https://pure.mpg.de/cone/journals/resource/2451-9456