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Superoxide radical and iron modulate aconitase activity in mammalian cells.
J Biol Chem. 1995 Jun 02; 270(22):13399-405.JB

Abstract

Aconitase is a member of a family of iron-sulfur-containing (de)hydratases whose activities are modulated in bacteria by superoxide radical (O2-.)-mediated inactivation and iron-dependent reactivation. The inactivation-reactivation of aconitase(s) in cultured mammalian cells was explored since these reactions may impact important and diverse aconitase functions in the cytoplasm and mitochondria. Conditions which increase O2-. production including exposure to the redox-cycling agent phenazine methosulfate (PMS), inhibitors of mitochondrial ubiquinol-cytochrome c oxidoreductase, or hyperoxia inactivated aconitase in mammalian cells. Overproduction of mitochondrial Mn-superoxide dismutase protected aconitase from inactivation by PMS or inhibitors of ubiquinol-cytochrome c oxidoreductase, but not from normobaric hyperoxia. Aconitase activity was reactivated (t1/2 of 12 +/- 3 min) upon removal of PMS. The iron chelator deferoxamine impaired reactivation and increased net inactivation of aconitase by O2-.. The ability of ubiquinol-cytochrome c oxidoreductase-generated O2-. to inactivate aconitase in several cell types correlated with the fraction of the aconitase activity localized in mitochondria. Extracellular O2-. generated with xanthine oxidase did not affect aconitase activity nor did exogenous superoxide dismutase decrease aconitase inactivation by PMS. The results demonstrate a dynamic and cyclical O2-.-mediated inactivation and iron-dependent reactivation of the mammalian [4Fe-4S] aconitases under normal and stress conditions and provide further evidence for the membrane compartmentalization of O2-..

Authors+Show Affiliations

Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7768942

Citation

Gardner, P R., et al. "Superoxide Radical and Iron Modulate Aconitase Activity in Mammalian Cells." The Journal of Biological Chemistry, vol. 270, no. 22, 1995, pp. 13399-405.
Gardner PR, Raineri I, Epstein LB, et al. Superoxide radical and iron modulate aconitase activity in mammalian cells. J Biol Chem. 1995;270(22):13399-405.
Gardner, P. R., Raineri, I., Epstein, L. B., & White, C. W. (1995). Superoxide radical and iron modulate aconitase activity in mammalian cells. The Journal of Biological Chemistry, 270(22), 13399-405.
Gardner PR, et al. Superoxide Radical and Iron Modulate Aconitase Activity in Mammalian Cells. J Biol Chem. 1995 Jun 2;270(22):13399-405. PubMed PMID: 7768942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Superoxide radical and iron modulate aconitase activity in mammalian cells. AU - Gardner,P R, AU - Raineri,I, AU - Epstein,L B, AU - White,C W, PY - 1995/6/2/pubmed PY - 1995/6/2/medline PY - 1995/6/2/entrez SP - 13399 EP - 405 JF - The Journal of biological chemistry JO - J Biol Chem VL - 270 IS - 22 N2 - Aconitase is a member of a family of iron-sulfur-containing (de)hydratases whose activities are modulated in bacteria by superoxide radical (O2-.)-mediated inactivation and iron-dependent reactivation. The inactivation-reactivation of aconitase(s) in cultured mammalian cells was explored since these reactions may impact important and diverse aconitase functions in the cytoplasm and mitochondria. Conditions which increase O2-. production including exposure to the redox-cycling agent phenazine methosulfate (PMS), inhibitors of mitochondrial ubiquinol-cytochrome c oxidoreductase, or hyperoxia inactivated aconitase in mammalian cells. Overproduction of mitochondrial Mn-superoxide dismutase protected aconitase from inactivation by PMS or inhibitors of ubiquinol-cytochrome c oxidoreductase, but not from normobaric hyperoxia. Aconitase activity was reactivated (t1/2 of 12 +/- 3 min) upon removal of PMS. The iron chelator deferoxamine impaired reactivation and increased net inactivation of aconitase by O2-.. The ability of ubiquinol-cytochrome c oxidoreductase-generated O2-. to inactivate aconitase in several cell types correlated with the fraction of the aconitase activity localized in mitochondria. Extracellular O2-. generated with xanthine oxidase did not affect aconitase activity nor did exogenous superoxide dismutase decrease aconitase inactivation by PMS. The results demonstrate a dynamic and cyclical O2-.-mediated inactivation and iron-dependent reactivation of the mammalian [4Fe-4S] aconitases under normal and stress conditions and provide further evidence for the membrane compartmentalization of O2-.. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/7768942/Superoxide_radical_and_iron_modulate_aconitase_activity_in_mammalian_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)92292-1 DB - PRIME DP - Unbound Medicine ER -