This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Singha, U. K.
Right arrow Articles by Chaudhuri, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singha, U. K.
Right arrow Articles by Chaudhuri, M.

 Previous Article  |  Next Article 

Eukaryotic Cell, September 2009, p. 1418-1428, Vol. 8, No. 9
1535-9778/09/$08.00+0     doi:10.1128/EC.00132-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Downregulation of Mitochondrial Porin Inhibits Cell Growth and Alters Respiratory Phenotype in Trypanosoma brucei{triangledown} ,{dagger}

Ujjal K. Singha, Shvetank Sharma, and Minu Chaudhuri*

Department of Microbial Pathogenesis and Immune Response, Meharry Medical College, Nashville, Tennessee 37208

Received 6 May 2009/ Accepted 10 July 2009

Porin is the most abundant outer membrane (OM) protein of mitochondria. It forms the aqueous channel on the mitochondrial OM and mediates major metabolite flux between mitochondria and cytosol. Mitochondrial porin in Trypanosoma brucei, a unicellular parasitic protozoan and the causative agent of African trypanosomiasis, possesses a β-barrel structure similar to the bacterial OM porin OmpA. T. brucei porin (TbPorin) is present as a monomer as well as an oligomer on the mitochondrial OM, and its expression is developmentally regulated. In spite of its distinct structure, the TbPorin function is similar to those of other eukaryotic porins. TbPorin RNA interference (RNAi) reduced cell growth in both procyclic and bloodstream forms. The depletion of TbPorin decreased ATP production by inhibiting metabolite flux through the OM. Additionally, the level of trypanosome alternative oxidase (TAO) decreased, whereas the levels of cytochrome-dependent respiratory complexes III and IV increased in TbPorin-depleted mitochondria. Furthermore, the depletion of TbPorin reduced cellular respiration via TAO, which is not coupled with oxidative phosphorylation, but increased the capacity for cyanide-sensitive respiration. Together, these data reveal that TbPorin knockdown reduced the mitochondrial ATP level, which in turn increased the capacity of the cytochrome-dependent respiratory pathway (CP), in an attempt to compensate for the mitochondrial energy crisis. However, a simultaneous decrease in the substrate-level phosphorylation due to TbPorin RNAi caused growth inhibition in the procyclic form. We also found that the expressions of TAO and CP proteins are coordinately regulated in T. brucei according to mitochondrial energy demand.

* Corresponding author. Mailing address: Department of Microbial Pathogenesis and Immune Response, Meharry Medical College, Nashville, TN 37208. Phone: (615) 327-5726. Fax: (615) 327-6072. E-mail: mchaudhuri{at}mmc.edu

{triangledown} Published ahead of print on 17 July 2009.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, September 2009, p. 1418-1428, Vol. 8, No. 9
1535-9778/09/$08.00+0     doi:10.1128/EC.00132-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»