1. Laboratory of Molecular Genetics, Department of Post-Genomics and Diseases,
2. Department of Otolaryngology and Sensory Organ Surgery and
3. Department of Internal Medicine and Therapeutics, Osaka University Medical school, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
4. Solution-Oriented Research for Science and Technology (SORST), Japan Science and Technology Corporation, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Correspondence to: Yoshihide Tsujimoto^1,4 Correspondence and requests for materials should be addressed to Y.T. (Email: tsujimot@gene.med.osaka-u.ac.jp).

Abstract

Mitochondria play an important role in energy production, Ca²⁺ homeostasis and cell death. In recent years, the role of the mitochondria in apoptotic and necrotic cell death has attracted much attention^{1, 2}. In apoptosis and necrosis, the mitochondrial permeability transition (mPT), which leads to disruption of the mitochondrial membranes and mitochondrial dysfunction, is considered to be one of the key events, although its exact role in cell death remains elusive. We therefore created mice lacking cyclophilin D (CypD), a protein considered to be involved in the mPT, to analyse its role in cell death. CypD-deficient mice were developmentally normal and showed no apparent anomalies, but CypD-deficient mitochondria did not undergo the cyclosporin A-sensitive mPT. CypD-deficient cells died normally in response to various apoptotic stimuli, but showed resistance to necrotic cell death induced by reactive oxygen species and Ca²⁺ overload. In addition, CypD-deficient mice showed a high level of resistance to ischaemia/reperfusion-induced cardiac injury. Our results indicate that the CypD-dependent mPT regulates some forms of necrotic death, but not apoptotic death.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.