HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.05-4204fjev1 20/8/1236    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Converso, D. P. Articles by Boczkowski, J. Search for Related Content PubMed PubMed Citation Articles by Converso, D. P. Articles by Boczkowski, J.

HO-1 is located in liver mitochondria and modulates mitochondrial heme content and metabolism

Daniela P. Converso^*, Camille Taillé, Maria Cecilia Carreras^*, Ariel Jaitovich^*, Juan José Poderoso^* and Jorge Boczkowski^,1

^* Laboratory of Oxygen Metabolism, University Hospital, University of Buenos Aires, Argentina; and

Institut National de la Santé et de la Recherche Médicale (INSERM U700), Université Paris 7, Faculté X. Bichat, Paris, France

¹Correspondence: INSERM U700 Faculté X. Bichat BP416, Paris 75870, Cedex 18, France. E-mail: jbb2{at}bichat.inserm.fr

ABSTRACT

This study investigated whether inducible HO-1 is targeted to mitochondria and its putative effects on oxidative metabolism in rat liver. Western blot and immune-electron microscopy in whole purified and fractionated organelles showed basal expression of HO-1 protein in both microsomes and mitochondria (inner membrane), accompanied by a parallel HO activity. Inducers of HO-1 increased HO-1 targeting to the inner mitochondrial membrane, which also contained biliverdin reductase, supporting that both enzymes are in the same compartmentalization. Induction of mitochondrial HO-1 was associated with a decrease of mitochondrial heme content and selective reduction of protein expression of cytochrome oxidase (COX) subunit I, which is coded by the mitochondrial genome and synthesized in the mitochondria depending on heme availability; these changes resulted in decreased COX spectrum and activity. Mitochondrial HO-1 induction was also associated with down-regulation of mitochondrial-targeted NO synthase expression and activity, resulting in a reduction of NO-dependent mitochondrial oxidant yield; inhibition of HO-1 activity reverted these effects. In conclusion, we demonstrated for the first time localization of HO-1 protein in mitochondria. It is surmised that mitochondrial HO-1 has important biological roles in regulating mitochondrial heme protein turnover and in protecting against conditions such as hypoxia, neurodegenerative diseases, or sepsis, in which substantially increased mitochondrial NO and oxidant production have been implicated.—Converso, D. P., Taillé, C., Carreras, M. C., Jaitovich, A., Poderoso, J. J., Boczkowski, J. HO-1 is located in liver mitochondria and modulates mitochondrial heme content and metabolism.

This article has been cited by other articles:

				A. L. Lagan, D. D. Melley, T. W. Evans, and G. J. Quinlan Pathogenesis of the systemic inflammatory syndrome and acute lung injury: role of iron mobilization and decompartmentalization Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L161 - L174. [Abstract] [Full Text] [PDF]

				D.-J. Slebos, S. W. Ryter, M. van der Toorn, F. Liu, F. Guo, C. J. Baty, J. M. Karlsson, S. C. Watkins, H. P. Kim, X. Wang, et al. Mitochondrial Localization and Function of Heme Oxygenase-1 in Cigarette Smoke-Induced Cell Death Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 409 - 417. [Abstract] [Full Text] [PDF]