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Pro‐oxidants and mitochondrial Ca 2+ : their relationship to apoptosis and oncogenesis
Author(s) -
Richter Christoph
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81423-w
Subject(s) - apoptosis , mitochondrion , microbiology and biotechnology , carcinogenesis , cytosol , biology , programmed cell death , apoptosis inducing factor , catalase , chemistry , biochemistry , gene , oxidative stress , caspase , enzyme
Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca 2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto‐oncogen bcl‐2 have an increased mitochondrial membrane potential (δψ), as have many carcinoma cells, bcl‐2 protects L929 cells against apoptosis caused by pro‐oxidant‐induced mitochondrial Ca 2+ ‘cycling’ and increased cytosolic Ca 2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca 2+ release also prevent apoptosis. It is suggested that a pro‐oxidant‐induced Ca 2+ release from mitochondria, followed by Ca 2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of δψ stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells.