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

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.

SUBMITTER: Ghosh JC

PROVIDER: S-EPMC2982903 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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

Ghosh Jagadish C JC Siegelin Markus D MD Dohi Takehiko T Altieri Dario C DC

Cancer research 20101026 22

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, sel ...[more]

PMID: 20978188

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