PMID- 25791316
OWN - NLM
STAT- MEDLINE
DCOM- 20160125
LR  - 20181113
IS  - 1872-9428 (Electronic)
IS  - 0166-6851 (Print)
IS  - 0166-6851 (Linking)
VI  - 199
IP  - 1-2
DP  - 2015 Jan-Feb
TI  - Down regulation of Tim50 in Trypanosoma brucei increases tolerance to oxidative 
      stress.
PG  - 9-18
LID - S0166-6851(15)00012-2 [pii]
LID - 10.1016/j.molbiopara.2015.03.002 [doi]
AB  - Trypanosoma brucei, the causative agent for African trypanosomiasis, possesses a 
      single mitochondrion that imports hundreds of proteins from the cytosol. However, 
      the parasite only possesses a few homologs of the canonical protein translocases 
      found in fungi and animals. We recently characterized a homolog of the 
      translocase of the mitochondrial inner membrane, Tim50, in T. brucei. TbTim50 
      knockdown (KD) moderately reduced cell growth, decreased the mitochondrial 
      membrane potential, and inhibited import of proteins into mitochondria. In 
      contrast to Tim50 KD, we show here that TbTim50 overexpression (OE) increased the 
      mitochondrial membrane potential as well as increased the production of cellular 
      reactive oxygen species (ROS). Therefore, TbTim50 OE also inhibits cell growth. 
      In addition, TbTim50 OE and KD cells showed different responses upon treatment 
      with H2O2. Surprisingly, TbTim50 KD cells showed a greater tolerance to oxidative 
      stress. Further analysis revealed that TbTim50 KD inhibits transition of cells 
      from an early to late apoptotic stage upon exposure to increasing concentrations 
      of H2O2. On the other hand TbTim50 OE caused cells to be in a pro-apoptotic stage 
      and thus they underwent increased cell death upon H2O2 treatment. However, 
      externally added H2O2 similarly increased the levels of cellular ROS and 
      decreased the mitochondrial membrane potential in both cell types, indicating 
      that tolerance to ROS is mediated through induction of the stress-response 
      pathway due to TbTim50 KD. Together, these results suggest that TbTim50 acts as a 
      stress sensor and that down regulation of Tim50 could be a survival mechanism for 
      T. brucei exposed to oxidative stress.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Fullerton, Marjorie
AU  - Fullerton M
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      TN, USA.
FAU - Singha, Ujjal K
AU  - Singha UK
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      TN, USA.
FAU - Duncan, Melanie
AU  - Duncan M
AD  - University of Pennsylvania, Philadelphia, USA.
FAU - Chaudhuri, Minu
AU  - Chaudhuri M
AD  - Department of Microbiology and Immunology, Meharry Medical College, Nashville, 
      TN, USA. Electronic address: mchaudhuri@mmc.edu.
LA  - eng
GR  - T32 HL007737/HL/NHLBI NIH HHS/United States
GR  - 2SC1GM081146/GM/NIGMS NIH HHS/United States
GR  - G12 MD007586/MD/NIMHD NIH HHS/United States
GR  - 5T32AI007281/AI/NIAID NIH HHS/United States
GR  - G12 RR003032/RR/NCRR NIH HHS/United States
GR  - 5T32HL007737/HL/NHLBI NIH HHS/United States
GR  - 2R25GM059994/GM/NIGMS NIH HHS/United States
GR  - T32 AI007281/AI/NIAID NIH HHS/United States
GR  - G12RR003032/RR/NCRR NIH HHS/United States
GR  - R25 GM059994/GM/NIGMS NIH HHS/United States
GR  - SC1 GM081146/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150316
PL  - Netherlands
TA  - Mol Biochem Parasitol
JT  - Molecular and biochemical parasitology
JID - 8006324
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.3.2.12 (Peptidyl Transferases)
SB  - IM
MH  - Cell Survival
MH  - Down-Regulation
MH  - *Gene Expression Regulation
MH  - Hydrogen Peroxide/toxicity
MH  - Membrane Potential, Mitochondrial
MH  - *Oxidative Stress
MH  - Peptidyl Transferases/*biosynthesis
MH  - Reactive Oxygen Species/metabolism
MH  - *Stress, Physiological
MH  - Trypanosoma brucei brucei/drug effects/genetics/growth & development/*physiology
PMC - PMC4430343
MID - NIHMS673430
OTO - NOTNLM
OT  - Apoptosis
OT  - Membrane potential
OT  - Mitochondria
OT  - Oxidative stress
OT  - T. brucei
OT  - TbTim50
EDAT- 2015/03/21 06:00
MHDA- 2016/01/26 06:00
PMCR- 2016/03/16
CRDT- 2015/03/21 06:00
PHST- 2014/09/23 00:00 [received]
PHST- 2015/03/06 00:00 [revised]
PHST- 2015/03/08 00:00 [accepted]
PHST- 2015/03/21 06:00 [entrez]
PHST- 2015/03/21 06:00 [pubmed]
PHST- 2016/01/26 06:00 [medline]
PHST- 2016/03/16 00:00 [pmc-release]
AID - S0166-6851(15)00012-2 [pii]
AID - 10.1016/j.molbiopara.2015.03.002 [doi]
PST - ppublish
SO  - Mol Biochem Parasitol. 2015 Jan-Feb;199(1-2):9-18. doi: 
      10.1016/j.molbiopara.2015.03.002. Epub 2015 Mar 16.