| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,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:
|
|
 |
|
  Z. Zhong, V. K. Ramshesh, H. Rehman, R. T. Currin, V. Sridharan, T. P. Theruvath, I. Kim, G. L. Wright, and J. J. Lemasters Activation of the oxygen-sensing signal cascade prevents mitochondrial injury after mouse liver ischemia-reperfusion Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G823 - G832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Goven, A Boutten, V Lecon-Malas, J Marchal-Somme, N Amara, B Crestani, M Fournier, G Leseche, P Soler, J Boczkowski, et al. Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema Thorax, October 1, 2008; 63(10): 916 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Chang, L. Wu, and R. Wang Inhibition of vascular smooth muscle cell proliferation by chronic hemin treatment Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H999 - H1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
