PMID- 32520929
OWN - NLM
STAT- MEDLINE
DCOM- 20200729
LR  - 20200729
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 18
IP  - 6
DP  - 2020 Jun
TI  - Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of 
      mitochondria to drive developmental progression of Trypanosoma brucei.
PG  - e3000741
LID - 10.1371/journal.pbio.3000741 [doi]
LID - e3000741
AB  - Mitochondrial metabolic remodeling is a hallmark of the Trypanosoma brucei 
      digenetic life cycle because the insect stage utilizes a cost-effective oxidative 
      phosphorylation (OxPhos) to generate ATP, while bloodstream cells switch to 
      aerobic glycolysis. Due to difficulties in acquiring enough parasites from the 
      tsetse fly vector, the dynamics of the parasite's metabolic rewiring in the 
      vector have remained obscure. Here, we took advantage of in vitro-induced 
      differentiation to follow changes at the RNA, protein, and metabolite levels. 
      This multi-omics and cell-based profiling showed an immediate redirection of 
      electron flow from the cytochrome-mediated pathway to an alternative oxidase 
      (AOX), an increase in proline consumption, elevated activity of complex II, and 
      certain tricarboxylic acid (TCA) cycle enzymes, which led to mitochondrial 
      membrane hyperpolarization and increased reactive oxygen species (ROS) levels. 
      Interestingly, these ROS molecules appear to act as signaling molecules driving 
      developmental progression because ectopic expression of catalase, a ROS 
      scavenger, halted the in vitro-induced differentiation. Our results provide 
      insights into the mechanisms of the parasite's mitochondrial rewiring and 
      reinforce the emerging concept that mitochondria act as signaling organelles 
      through release of ROS to drive cellular differentiation.
FAU - Dolezelova, Eva
AU  - Dolezelova E
AD  - Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske 
      Budejovice, Czech Republic.
FAU - Kunzova, Michaela
AU  - Kunzova M
AD  - Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske 
      Budejovice, Czech Republic.
AD  - Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech 
      Republic.
FAU - Dejung, Mario
AU  - Dejung M
AUID- ORCID: 0000-0002-0509-0207
AD  - Institute of Molecular Biology (IMB), Mainz, Germany.
FAU - Levin, Michal
AU  - Levin M
AD  - Institute of Molecular Biology (IMB), Mainz, Germany.
FAU - Panicucci, Brian
AU  - Panicucci B
AD  - Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske 
      Budejovice, Czech Republic.
FAU - Regnault, Clement
AU  - Regnault C
AD  - Welcome Centre for Integrative Parasitology, Institute of Infection, Immunity and 
      Inflammation, Glasgow Polyomics, College of Medical, Veterinary and Life 
      Sciences, University of Glasgow, Glasgow, United Kingdom.
FAU - Janzen, Christian J
AU  - Janzen CJ
AD  - Welcome Centre for Integrative Parasitology, Institute of Infection, Immunity and 
      Inflammation, Glasgow Polyomics, College of Medical, Veterinary and Life 
      Sciences, University of Glasgow, Glasgow, United Kingdom.
FAU - Barrett, Michael P
AU  - Barrett MP
AD  - Department of Cell and Developmental Biology, Biocenter, University Wuerzburg, 
      Wuerzburg, Germany.
FAU - Butter, Falk
AU  - Butter F
AUID- ORCID: 0000-0002-7197-7279
AD  - Institute of Molecular Biology (IMB), Mainz, Germany.
FAU - Zikova, Alena
AU  - Zikova A
AUID- ORCID: 0000-0002-8686-0225
AD  - Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske 
      Budejovice, Czech Republic.
AD  - Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech 
      Republic.
LA  - eng
GR  - 104111/Z/14/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200610
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Plant Proteins)
RN  - 0 (Proteome)
RN  - 0 (Protozoan Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.- (alternative oxidase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Cell Differentiation/drug effects
MH  - Cell Line
MH  - Cell Respiration/drug effects
MH  - Electron Transport/drug effects
MH  - Electrons
MH  - Glucose/pharmacology
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Metabolic Networks and Pathways/drug effects
MH  - *Metabolomics
MH  - Mitochondria/drug effects/*metabolism
MH  - Mitochondrial Proteins/metabolism
MH  - Oxidation-Reduction
MH  - Oxidoreductases/metabolism
MH  - Plant Proteins/metabolism
MH  - Proline/metabolism
MH  - Proteome/metabolism
MH  - Protozoan Proteins/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Transcriptome/genetics
MH  - Trypanosoma brucei brucei/drug effects/genetics/*growth & development/*metabolism
PMC - PMC7307792
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/06/11 06:00
MHDA- 2020/07/30 06:00
PMCR- 2020/06/10
CRDT- 2020/06/11 06:00
PHST- 2019/12/04 00:00 [received]
PHST- 2020/05/27 00:00 [accepted]
PHST- 2020/06/22 00:00 [revised]
PHST- 2020/06/11 06:00 [pubmed]
PHST- 2020/07/30 06:00 [medline]
PHST- 2020/06/11 06:00 [entrez]
PHST- 2020/06/10 00:00 [pmc-release]
AID - PBIOLOGY-D-19-03519 [pii]
AID - 10.1371/journal.pbio.3000741 [doi]
PST - epublish
SO  - PLoS Biol. 2020 Jun 10;18(6):e3000741. doi: 10.1371/journal.pbio.3000741. 
      eCollection 2020 Jun.