Heat shock protein 60 regulation of the mitochondrial permeability transition pore in tumor cells

Jagadish C. Ghosh, Markus D. Siegelin, Takehiko Dohi, Dario C. Altieri

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Mitochondrial apoptosis plays a critical role in tumor maintenance and dictates the response to therapy in vivo; however, the regulators of this process are still largely elusive. Here, we show that the molecular chaperone heat shock protein 60 (Hsp60) directly associates with cyclophilin D (CypD), a component of the mitochondrial permeability transition pore. This interaction occurs in a multichaperone complex comprising Hsp60, Hsp90, and tumor necrosis factor receptor-associated protein-1, selectively assembled in tumor but not in normal mitochondria. Genetic targeting of Hsp60 by siRNA triggers CypD-dependent mitochondrial permeability transition, caspase-dependent apoptosis, and suppression of intracranial glioblastoma growth in vivo. Therefore, Hsp60 is a novel regulator of mitochondrial permeability transition, contributing to a cytoprotective chaperone network that antagonizes CypD-dependent cell death in tumors.

Original languageEnglish (US)
Pages (from-to)8988-8993
Number of pages6
JournalCancer Research
Volume70
Issue number22
DOIs
StatePublished - Nov 15 2010

Fingerprint

Chaperonin 60
Permeability
Neoplasms
Apoptosis
Molecular Chaperones
Tumor Necrosis Factor Receptors
Glioblastoma
Caspases
Small Interfering RNA
Mitochondria
Cell Death
Maintenance
mitochondrial permeability transition pore
Growth
cyclophilin D
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Ghosh, Jagadish C. ; Siegelin, Markus D. ; Dohi, Takehiko ; Altieri, Dario C. / Heat shock protein 60 regulation of the mitochondrial permeability transition pore in tumor cells. In: Cancer Research. 2010 ; Vol. 70, No. 22. pp. 8988-8993.
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Heat shock protein 60 regulation of the mitochondrial permeability transition pore in tumor cells. / Ghosh, Jagadish C.; Siegelin, Markus D.; Dohi, Takehiko; Altieri, Dario C.

In: Cancer Research, Vol. 70, No. 22, 15.11.2010, p. 8988-8993.

Research output: Contribution to journalArticle

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