MITOCHONDRIAL PROTEIN IMPORT IN AFRICAN TRYPANOSOMES

Summary

Principal Investigator: Minu Chaudhuri
Abstract: DESCRIPTION (Adapted from applicant's abstract) Blood borne parasitic disease are major causes of human morbidity and mortality, particularly in the tropical world. African trypanosomes, the protozoa of the Trypanosoma brucei complex, are such parasites that live extracellularly in the blood and tissue fluids of the vertebrate host, utilizing blood glucose as their sole source of energy eventually leading to hypoglycemia and disease syndrome known as African sleeping sickness. Mitochondrial biogenesis is an essential part of the digenetic life cycle of this protozoa. These cells suppress their mitochondrial activities when they live in the bloodstream of its mammalian host. During bloodmeal, parasites are transferred to the insect gut and there they regenerate their mitochondrial activities. Import of a vast majority of nuclear encoded mitochondrial protein is a necessary process for mitochondrial biogenesis. The goal of this study is to characterize mitochondrial protein import mechanisms in African trypanosomes so as to understand their roles in mitochondrial biogenesis. The initial requirement to accomplish this goal is the isolation and characterization of the trypanosome proteins involved in mitochondrial protein import. The specific aims of this proposal are: 1) to identify and characterize the receptors that import proteins across the outer mitochondrial membrane from T. Brucei; and to assess whether they are differentially expressed during the parasite life cycle; 2) to clone and characterize components of the TOM complex (TOM70, TOM40, TOM22, and TOM20) from T. Brucei; and 3) to study the roles of these cloned proteins in the import of the recombinant trypanosome alternative oxidase protein into isolated mitochondria of T. brucei. Characterization of the mitochondrial import machinery in this parasite may provide insight into genetic control mechanisms in trypanosomes where, in contrast to most eukaryotes, developmental regulation of gene expression is almost entirely post-transcriptional. Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies.
Funding Period: 1998-06-01 - 2004-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Protein phosphatase 5 is required for Hsp90 function during proteotoxic stresses in Trypanosoma brucei
    Candace Jones
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Parasitol Res 102:835-44. 2008
  2. ncbi The effect of over-expression of the alternative oxidase in the procyclic forms of Trypanosoma brucei
    Robert Walker
    Department of Microbiology, Meharry Medical College, Nashville, TN 37208, USA
    Mol Biochem Parasitol 139:153-62. 2005
  3. ncbi The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria
    Minu Chaudhuri
    Department of Microbiology, School of Medicine, Meharry Medical College, Nashville, TN, 37208, USA
    Parasitol Res 96:178-83. 2005
  4. ncbi Trypanosome alternative oxidase: from molecule to function
    Minu Chaudhuri
    Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, Meharry Medical College, Nashville, TN 37208, USA
    Trends Parasitol 22:484-91. 2006
  5. ncbi Functional characterization of the serine/threonine protein phosphatase 5 from Trypanosoma brucei
    Sedrick Anderson
    Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, Meharry Medical College, Nashville, Tennessee 37208, USA
    J Parasitol 92:1152-61. 2006
  6. pmc Trypanosoma brucei: differential requirement of membrane potential for import of proteins into mitochondria in two developmental stages
    Shuntae Williams
    Department of Microbial Pathogenesis and Immune Response, School of Medicine, Meharry Medical College, 1005 D B Todd Jr Boulevard, Nashville, TN 37208, USA
    Exp Parasitol 118:420-33. 2008
  7. pmc Characterization of the mitochondrial inner membrane protein translocator Tim17 from Trypanosoma brucei
    Ujjal K Singha
    Department of Microbial Pathogenesis and Immune Response, Meharry Medical College, Nashville, TN 37208, USA
    Mol Biochem Parasitol 159:30-43. 2008

Scientific Experts

  • Minu Chaudhuri
  • Ujjal K Singha
  • Lipi Saha
  • Shuntae Williams
  • Candace Jones
  • Sedrick Anderson
  • Robert Walker
  • Emmanuel Peprah
  • George C Hill

Detail Information

Publications7

  1. ncbi Protein phosphatase 5 is required for Hsp90 function during proteotoxic stresses in Trypanosoma brucei
    Candace Jones
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Parasitol Res 102:835-44. 2008
    ..Together, these results suggest that TbPP5 positively regulates the function of Hsp90 to maintain cellular homeostasis during proteotoxic stresses in T. brucei...
  2. ncbi The effect of over-expression of the alternative oxidase in the procyclic forms of Trypanosoma brucei
    Robert Walker
    Department of Microbiology, Meharry Medical College, Nashville, TN 37208, USA
    Mol Biochem Parasitol 139:153-62. 2005
    ..This suggests that the expression of two terminal oxidases and the coat protein is linked in T. brucei...
  3. ncbi The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei mitochondria
    Minu Chaudhuri
    Department of Microbiology, School of Medicine, Meharry Medical College, Nashville, TN, 37208, USA
    Parasitol Res 96:178-83. 2005
    ..However, it exists as a monomer in Trypanosoma brucei mitochondria...
  4. ncbi Trypanosome alternative oxidase: from molecule to function
    Minu Chaudhuri
    Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, Meharry Medical College, Nashville, TN 37208, USA
    Trends Parasitol 22:484-91. 2006
    ..Alternative oxidases similar to TAO have been found in a wide variety of organisms but not in mammals, thus rendering TAO an important chemotherapeutic target for African trypanosomiasis...
  5. ncbi Functional characterization of the serine/threonine protein phosphatase 5 from Trypanosoma brucei
    Sedrick Anderson
    Division of Microbial Pathogenesis and Immune Response, Department of Biomedical Sciences, Meharry Medical College, Nashville, Tennessee 37208, USA
    J Parasitol 92:1152-61. 2006
    ..brucei. Taken together; these findings suggest that a serum factor (or factors) induces up-regulation of TbPP5 expression during the G1 phase, which is required for proper cell growth...
  6. pmc Trypanosoma brucei: differential requirement of membrane potential for import of proteins into mitochondria in two developmental stages
    Shuntae Williams
    Department of Microbial Pathogenesis and Immune Response, School of Medicine, Meharry Medical College, 1005 D B Todd Jr Boulevard, Nashville, TN 37208, USA
    Exp Parasitol 118:420-33. 2008
    ..Differential import conditions of nuclear encoded mitochondrial proteins of T. brucei possibly help it to adapt to different life forms...
  7. pmc Characterization of the mitochondrial inner membrane protein translocator Tim17 from Trypanosoma brucei
    Ujjal K Singha
    Department of Microbial Pathogenesis and Immune Response, Meharry Medical College, Nashville, TN 37208, USA
    Mol Biochem Parasitol 159:30-43. 2008
    ..Together, these show that TbTim17 is the translocator of nuclear encoded mitochondrial proteins and its expression is regulated according to mitochondrial activities in T. brucei...