2. Academic Validation
  3. Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for Myrtucommulone

Mitochondrial Chaperonin HSP60 Is the Apoptosis-Related Target for Myrtucommulone

  • Cell Chem Biol. 2017 May 18;24(5):614-623.e6. doi: 10.1016/j.chembiol.2017.04.008.
Katja Wiechmann 1,  Hans Müller 2,  Stefanie König 1,  Natalie Wielsch 3,  Aleš Svatoš 3,  Johann Jauch 2,  Oliver Werz 4
Affiliations

Affiliations

  • 1 Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Philosophenweg 14, 07743 Jena, Germany.
  • 2 Organic Chemistry II, Saarland University, Campus C 4.2, 66123 Saarbrücken, Germany.
  • 3 Research Group Mass Spectrometry and Proteomics, Max Planck Institute for Chemical Ecology, Hans-Knöll-Straße 8, 07745 Jena, Germany.
  • 4 Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, University of Jena, Philosophenweg 14, 07743 Jena, Germany. Electronic address: oliver.werz@uni-jena.de.
PMID: 28457707 DOI: 10.1016/j.chembiol.2017.04.008
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 using MC 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.

Keywords

Lon protease-like protein; apoptosis; heat-shock protein 60; mitochondria; myrtucommulone; target fishing.

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