Ca2+ release from mitochondria induced by prooxidants.
A variety of chemically different prooxidants causes Ca2+ release from mitochondria. The prooxidant-induced Ca2+ release occurs from intact mitochondria via a route which is physiologically relevant and may be regulated by protein ADP-ribosylation. When the released Ca2+ is excessively cycled by mitochondria they are damaged. This leads to uncoupling, a decreased ATP supply, and a decreased ability of mitochondria to retain Ca2+. Excessive Ca2+ cycling by mitochondria will deprive cells of ATP. As a result, Ca2+ ATPases of the endoplasmic (sarcoplasmic) reticulum and the plasma membrane are stopped. The rising cytosolic Ca2+ level cannot be counterbalanced due to damage of mitochondria which, under normoxic conditions, act as safety device against increased cytosolic Ca2+. It is proposed that prooxidants are toxic because they impair the ability of mitochondria to retain Ca2+.
Richter
C
C
Laboratory of Biochemistry, Swiss Federal Institute of Technology, Zurich.
Frei
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005609:Free Radicals; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction
D005609:Free Radicals; D002118:Calcium