Role of iron and ferritin in TNFα-induced apoptosis in HeLa cells

We found that tumor necrosis factor alpha (TNFalpha)-induced apoptosis in HeLa cells was accompanied by a similar to2-fold increase in H- and L-ferritin and a decrease in transferrin receptor, two indices of increased iron availability. Iron supplementation and overexpression of H-ferritin or its mutant with an inactivated ferroxidase center reduced by about similar to50% the number of apoptotic cells after TNFalpha-treatment, while overexpression of L-ferritin was ineffective. The data indicate that H-ferritin has an anti-apoptotic activity unrelated to its ferroxidase activity and to its capacity to modify cellular iron metabolism. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.