Landscape of the mitochondrial Hsp90 metabolome in tumours.

Authors

Young Chan Chae, The Wistar Institute, Philadelphia, PAFollow
Alessia Angelin, Children’s Hospital of Philadelphia, Philadelphia, PA
Sofia Lisanti, The Wistar Institute, Philadelphia, PAFollow
Andrew V Kossenkov, The Wistar Institute, Philadelphia, PAFollow
Kaye D Speicher, The Wistar Institute, Philadelphia, PA
Huan Wang, The Wistar Institute, Philadelphia, PA
James F Powers, Tufts Medical Center, Boston, MA
Arthur S Tischler, Tufts Medical Center, Boston, MAFollow
Karel Pacak, National Institutes of Health, Bethesda, MD
Stephanie Fliedner, National Institutes of Health, Bethesda, MD
Ryan D Michalek, Metabolon, Inc. Durham, NC
Edward D Karoly, Metabolon, Inc. Durham, NC
Douglas C Wallace, Children’s Hospital of Philadelphia, Philadelphia, PAFollow
Lucia R Languino, Department of Cancer Biology, Prostate Cancer Discovery and Development Program, Thomas Jefferson UniversityFollow
David W Speicher, The Wistar Institute, Philadelphia, PAFollow
Dario C Altieri, The Wistar Institute, Philadelphia, PAFollow

Document Type

Article

Publication Date

1-1-2013

Comments

This article has been peer reviewed. It was published in: Nature Communications.

2013 July 10; 4: 2139.

The published version is available at DOI: 10.1038/ncomms3139. Copyright © Nature

Abstract

Reprogramming of tumour cell metabolism contributes to disease progression and resistance to therapy, but how this process is regulated on the molecular level is unclear. Here we report that heat shock protein 90-directed protein folding in mitochondria controls central metabolic networks in tumour cells, including the electron transport chain, citric acid cycle, fatty acid oxidation, amino acid synthesis and cellular redox status. Specifically, mitochondrial heat shock protein 90, but not cytosolic heat shock protein 90, binds and stabilizes the electron transport chain Complex II subunit succinate dehydrogenase-B, maintaining cellular respiration under low-nutrient conditions, and contributing to hypoxia-inducible factor-1α-mediated tumorigenesis in patients carrying succinate dehydrogenase-B mutations. Thus, heat shock protein 90-directed proteostasis in mitochondria regulates tumour cell metabolism, and may provide a tractable target for cancer therapy.

Recommended Citation

Chae, Young Chan; Angelin, Alessia; Lisanti, Sofia; Kossenkov, Andrew V; Speicher, Kaye D; Wang, Huan; Powers, James F; Tischler, Arthur S; Pacak, Karel; Fliedner, Stephanie; Michalek, Ryan D; Karoly, Edward D; Wallace, Douglas C; Languino, Lucia R; Speicher, David W; and Altieri, Dario C, "Landscape of the mitochondrial Hsp90 metabolome in tumours." (2013). Kimmel Cancer Center Faculty Papers. Paper 46.
https://jdc.jefferson.edu/kimmelccfp/46

PubMed ID

23842546