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Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion.
Proc Natl Acad Sci U S A. 2005 Apr 26; 102(17):5987-91.PN

Abstract

Prooxidents can induce reversible inhibition or irreversible inactivation and degradation of the mitochondrial enzyme aconitase. Cardiac ischemia/reperfusion is associated with an increase in mitochondrial free radical production. In the current study, the effects of reperfusion-induced production of prooxidants on mitochondrial aconitase and proteolytic activity were determined to assess whether alterations represented a regulated response to changes in redox status or oxidative damage. Evidence is provided that ATP-dependent proteolytic activity increased during early reperfusion followed by a time-dependent reduction in activity to control levels. These alterations in proteolytic activity paralleled an increase and subsequent decrease in the level of oxidatively modified protein. In vitro data supports a role for prooxidants in the activation of ATP-dependent proteolytic activity. Despite inhibition during early periods of reperfusion, aconitase was not degraded under the conditions of these experiments. Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion. Loss and regain in activity involved reversible sulfhydryl modification. Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion. In vitro, frataxin has been shown to protect aconitase from [4Fe-4S](2+) cluster disassembly, irreversible inactivation, and, potentially, degradation. Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusion-induced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria.

Authors+Show Affiliations

Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4970, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15840721

Citation

Bulteau, Anne-Laure, et al. "Reversible Redox-dependent Modulation of Mitochondrial Aconitase and Proteolytic Activity During in Vivo Cardiac Ischemia/reperfusion." Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 17, 2005, pp. 5987-91.
Bulteau AL, Lundberg KC, Ikeda-Saito M, et al. Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. Proc Natl Acad Sci U S A. 2005;102(17):5987-91.
Bulteau, A. L., Lundberg, K. C., Ikeda-Saito, M., Isaya, G., & Szweda, L. I. (2005). Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. Proceedings of the National Academy of Sciences of the United States of America, 102(17), 5987-91.
Bulteau AL, et al. Reversible Redox-dependent Modulation of Mitochondrial Aconitase and Proteolytic Activity During in Vivo Cardiac Ischemia/reperfusion. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5987-91. PubMed PMID: 15840721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. AU - Bulteau,Anne-Laure, AU - Lundberg,Kathleen C, AU - Ikeda-Saito,Masao, AU - Isaya,Grazia, AU - Szweda,Luke I, Y1 - 2005/04/19/ PY - 2005/4/21/pubmed PY - 2005/7/9/medline PY - 2005/4/21/entrez SP - 5987 EP - 91 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 102 IS - 17 N2 - Prooxidents can induce reversible inhibition or irreversible inactivation and degradation of the mitochondrial enzyme aconitase. Cardiac ischemia/reperfusion is associated with an increase in mitochondrial free radical production. In the current study, the effects of reperfusion-induced production of prooxidants on mitochondrial aconitase and proteolytic activity were determined to assess whether alterations represented a regulated response to changes in redox status or oxidative damage. Evidence is provided that ATP-dependent proteolytic activity increased during early reperfusion followed by a time-dependent reduction in activity to control levels. These alterations in proteolytic activity paralleled an increase and subsequent decrease in the level of oxidatively modified protein. In vitro data supports a role for prooxidants in the activation of ATP-dependent proteolytic activity. Despite inhibition during early periods of reperfusion, aconitase was not degraded under the conditions of these experiments. Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion. Loss and regain in activity involved reversible sulfhydryl modification. Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion. In vitro, frataxin has been shown to protect aconitase from [4Fe-4S](2+) cluster disassembly, irreversible inactivation, and, potentially, degradation. Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusion-induced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/15840721/Reversible_redox_dependent_modulation_of_mitochondrial_aconitase_and_proteolytic_activity_during_in_vivo_cardiac_ischemia/reperfusion_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=15840721 DB - PRIME DP - Unbound Medicine ER -