• Je něco špatně v tomto záznamu ?

Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei

E. Doleželová, M. Kunzová, M. Dejung, M. Levin, B. Panicucci, C. Regnault, CJ. Janzen, MP. Barrett, F. Butter, A. Zíková,

. 2020 ; 18 (6) : e3000741. [pub] 20200610

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20024961

Grantová podpora
104111/Z/14/Z Wellcome Trust - United Kingdom

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc20024961
003      
CZ-PrNML
005      
20201222154950.0
007      
ta
008      
201125s2020 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1371/journal.pbio.3000741 $2 doi
035    __
$a (PubMed)32520929
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Doleželová, Eva $u Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic.
245    10
$a Cell-based and multi-omics profiling reveals dynamic metabolic repurposing of mitochondria to drive developmental progression of Trypanosoma brucei / $c E. Doleželová, M. Kunzová, M. Dejung, M. Levin, B. Panicucci, C. Regnault, CJ. Janzen, MP. Barrett, F. Butter, A. Zíková,
520    9_
$a 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.
650    _2
$a adenosintrifosfát $x biosyntéza $7 D000255
650    _2
$a buněčná diferenciace $x účinky léků $7 D002454
650    _2
$a buněčné linie $7 D002460
650    _2
$a buněčné dýchání $x účinky léků $7 D019069
650    _2
$a transport elektronů $x účinky léků $7 D004579
650    _2
$a elektrony $7 D004583
650    _2
$a glukosa $x farmakologie $7 D005947
650    _2
$a membránový potenciál mitochondrií $x účinky léků $7 D053078
650    _2
$a metabolické sítě a dráhy $x účinky léků $7 D053858
650    12
$a metabolomika $7 D055432
650    _2
$a mitochondrie $x účinky léků $x metabolismus $7 D008928
650    _2
$a mitochondriální proteiny $x metabolismus $7 D024101
650    _2
$a oxidace-redukce $7 D010084
650    _2
$a oxidoreduktasy $x metabolismus $7 D010088
650    _2
$a rostlinné proteiny $x metabolismus $7 D010940
650    _2
$a prolin $x metabolismus $7 D011392
650    _2
$a proteom $x metabolismus $7 D020543
650    _2
$a protozoální proteiny $x metabolismus $7 D015800
650    _2
$a reaktivní formy kyslíku $x metabolismus $7 D017382
650    _2
$a signální transdukce $7 D015398
650    _2
$a transkriptom $x genetika $7 D059467
650    _2
$a Trypanosoma brucei brucei $x účinky léků $x genetika $x růst a vývoj $x metabolismus $7 D014346
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Kunzová, Michaela $u Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic. Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic.
700    1_
$a Dejung, Mario $u Institute of Molecular Biology (IMB), Mainz, Germany.
700    1_
$a Levin, Michal $u Institute of Molecular Biology (IMB), Mainz, Germany.
700    1_
$a Panicucci, Brian $u Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic.
700    1_
$a Regnault, Clément $u 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.
700    1_
$a Janzen, Christian J $u 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.
700    1_
$a Barrett, Michael P $u Department of Cell and Developmental Biology, Biocenter, University Wuerzburg, Wuerzburg, Germany.
700    1_
$a Butter, Falk $u Institute of Molecular Biology (IMB), Mainz, Germany.
700    1_
$a Zíková, Alena $u Institute of Parasitology, Biology Centre, Czech Academy of Sciences, Ceske Budejovice, Czech Republic. Faculty of Science, University of South Bohemia, Ceske Budejovice, Czech Republic.
773    0_
$w MED00008061 $t PLoS biology $x 1545-7885 $g Roč. 18, č. 6 (2020), s. e3000741
856    41
$u https://pubmed.ncbi.nlm.nih.gov/32520929 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20201125 $b ABA008
991    __
$a 20201222154946 $b ABA008
999    __
$a ok $b bmc $g 1599106 $s 1115647
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2020 $b 18 $c 6 $d e3000741 $e 20200610 $i 1545-7885 $m PLoS biology $n Plos Biol $x MED00008061
GRA    __
$a 104111/Z/14/Z $p Wellcome Trust $2 United Kingdom
LZP    __
$a Pubmed-20201125

Najít záznam

Citační ukazatele

Možnosti archivace