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Is p53 the Long-Sought Molecular Trigger for Cyclophilin D-Regulated Mitochondrial Permeability Transition Pore Formation and Necrosis?

Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center, 240, Albert Sabin Way, Cincinnati, OH 45229-3039. .
Circulation Research (Impact Factor: 11.09). 10/2012; 111(10):1258-60. DOI: 10.1161/CIRCRESAHA.112.280990
Source: PubMed

ABSTRACT An article recently published in Cell concluded that p53 is necessary and sufficient to induce mitochondrial permeability transition pore (MPTP)-dependent necrosis through inducible p53 translocation to the matrix with cyclophilin D (CypD) binding. The results and implications are very provocative. The physiological significance of the proposed paradigm, however, is uncertain because calcium itself, which is a fundamental regulator of MPTP, is independent of p53, as shown by the authors. In addition, purified mitochondria from any unstimulated cell type or tissue, which presumably lacks p53 given the inducible mechanism proposed, have a fully functional MPTP to all the classic modes of stimulation as analyzed in vitro.

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