Oxidative stress in mitochondria: its relationship to cellular Ca2+ homeostasis, cell death, proliferation, and differentiation.
A variety of chemically different prooxidants causes Ca2+ release from mitochondria. This prooxidant-induced Ca2+ release occurs from intact mitochondria via a route which is physiologically relevant and may be regulated by protein monoADP-ribosylation. When the released Ca2+ is excessively 'cycled' by mitochondria (continuously taken up and released) the inner membrane is damaged. This leads to a decreased ability of mitochondria to retain Ca2+, uncoupling of mitochondria, and an impairment of ATP synthesis, which in turn deprives the cell of the energy necessary for the proper functioning of the Ca2+ ATPases of the endoplasmic (sarcoplasmic) reticulum, the nucleus and the plasma membrane. The ensuing rise of the cytosolic Ca2+ level cannot be counterbalanced by the damaged mitochondria which, under normoxic conditions, act as a safety device against an increase of the cytosolic Ca2+ concentration. The impaired ability of mitochondria to retain Ca2+ may lead to cell death. However, there is also evidence emerging that release of Ca2+ from mitochondria may be physiologically important for cell proliferation and differentiation.
Richter
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Swiss Federal Institute of Technology (ETH), Zurich.
Kass
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GE
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D006706:Homeostasis; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D014812:Vitamin K / Q000378:metabolism
D014812:Vitamin K; D000246:Adenosine Diphosphate Ribose; D000496:Alloxan; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium