-
Je něco špatně v tomto záznamu ?
Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe-S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei
E. Horáková, P. Changmai, Z. Paris, D. Salmon, J. Lukeš,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Free Medical Journals
od 2005 do Před 1 rokem
Medline Complete (EBSCOhost)
od 2005-01-01 do Před 1 rokem
Wiley Free Content
od 2005 do Před 1 rokem
PubMed
26277108
DOI
10.1111/febs.13411
Knihovny.cz E-zdroje
- MeSH
- ABC transportéry antagonisté a inhibitory genetika metabolismus MeSH
- akonitáthydratasa metabolismus MeSH
- biologické modely MeSH
- cytosol metabolismus MeSH
- fumarasa metabolismus MeSH
- fylogeneze MeSH
- genový knockdown MeSH
- hem metabolismus MeSH
- mitochondrie metabolismus MeSH
- proteiny obsahující železo a síru metabolismus MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům antagonisté a inhibitory genetika metabolismus MeSH
- protozoální geny MeSH
- protozoální proteiny antagonisté a inhibitory genetika metabolismus MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- testy genetické komplementace MeSH
- Trypanosoma brucei brucei genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
ABC transporter mitochondrial 1 (Atm1) and multidrug resistance-like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron-sulfur (Fe-S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe-S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe-S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe-S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Δatm1 and Δmdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc16020382
- 003
- CZ-PrNML
- 005
- 20160805120638.0
- 007
- ta
- 008
- 160722s2015 enk f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1111/febs.13411 $2 doi
- 024 7_
- $a 10.1111/febs.13411 $2 doi
- 035 __
- $a (PubMed)26277108
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a enk
- 100 1_
- $a Horáková, Eva $u Biology Centre, Institute of Parasitology, Czech Academy of Sciences, České Budějovice (Budweis), Czech Republic.
- 245 10
- $a Simultaneous depletion of Atm and Mdl rebalances cytosolic Fe-S cluster assembly but not heme import into the mitochondrion of Trypanosoma brucei / $c E. Horáková, P. Changmai, Z. Paris, D. Salmon, J. Lukeš,
- 520 9_
- $a ABC transporter mitochondrial 1 (Atm1) and multidrug resistance-like 1 (Mdl) are mitochondrial ABC transporters. Although Atm1 was recently suggested to transport different forms of glutathione from the mitochondrion, which are used for iron-sulfur (Fe-S) cluster maturation in the cytosol, the function of Mdl remains elusive. In Trypanosoma brucei, we identified one homolog of each of these genes, TbAtm and TbMdl, which were downregulated either separately or simultaneously using RNA interference. Individual depletion of TbAtm and TbMdl led to limited growth defects. In cells downregulated for TbAtm, the enzymatic activities of the Fe-S cluster proteins aconitase and fumarase significantly decreased in the cytosol but not in the mitochondrion. Downregulation of TbMdl did not cause any change in activities of the Fe-S proteins. Unexpectedly, the simultaneous downregulation of TbAtm and TbMdl did not result in any growth defect, nor were the Fe-S cluster protein activities altered in either the cytosolic or mitochondrial compartments. Additionally, TbAtm and TbMdl were able to partially restore the growth of the Saccharomyces cerevisiae Δatm1 and Δmdl2 null mutants, respectively. Because T. brucei completely lost the heme b biosynthesis pathway, this cofactor has to be obtained from the host. Based on our results, TbMdl is a candidate for mitochondrial import of heme b, which was markedly decreased in both TbMdl and TbAtm + TbMdl knockdowns. Moreover, the levels of heme a were strongly decreased in the same knockdowns, suggesting that TbMdl plays a key role in heme a biosynthesis, thus affecting the overall heme homeostasis in T. brucei.
- 650 _2
- $a ABC transportéry $x antagonisté a inhibitory $x genetika $x metabolismus $7 D018528
- 650 _2
- $a akonitáthydratasa $x metabolismus $7 D000154
- 650 _2
- $a cytosol $x metabolismus $7 D003600
- 650 _2
- $a fumarasa $x metabolismus $7 D005649
- 650 _2
- $a genový knockdown $7 D055785
- 650 _2
- $a protozoální geny $7 D017125
- 650 _2
- $a testy genetické komplementace $7 D005816
- 650 _2
- $a hem $x metabolismus $7 D006418
- 650 _2
- $a proteiny obsahující železo a síru $x metabolismus $7 D007506
- 650 _2
- $a mitochondrie $x metabolismus $7 D008928
- 650 _2
- $a biologické modely $7 D008954
- 650 _2
- $a proteiny spojené s mnohočetnou rezistencí k lékům $x antagonisté a inhibitory $x genetika $x metabolismus $7 D027425
- 650 _2
- $a fylogeneze $7 D010802
- 650 _2
- $a protozoální proteiny $x antagonisté a inhibitory $x genetika $x metabolismus $7 D015800
- 650 _2
- $a Saccharomyces cerevisiae $x genetika $x metabolismus $7 D012441
- 650 _2
- $a Trypanosoma brucei brucei $x genetika $x metabolismus $7 D014346
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Changmai, Piya $u Biology Centre, Institute of Parasitology, Czech Academy of Sciences, České Budějovice (Budweis), Czech Republic. Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic.
- 700 1_
- $a Paris, Zdeněk $u Biology Centre, Institute of Parasitology, Czech Academy of Sciences, České Budějovice (Budweis), Czech Republic.
- 700 1_
- $a Salmon, Didier $u Institute of Medical Biochemistry Leopoldo de Meis, Centro de Ciências e da Saude, Federal University of Rio de Janeiro, Brazil.
- 700 1_
- $a Lukeš, Julius $u Biology Centre, Institute of Parasitology, Czech Academy of Sciences, České Budějovice (Budweis), Czech Republic. Faculty of Sciences, University of South Bohemia, České Budějovice (Budweis), Czech Republic. Canadian Institute for Advanced Research, Toronto, Ontario, Canada.
- 773 0_
- $w MED00008414 $t The FEBS journal $x 1742-4658 $g Roč. 282, č. 21 (2015), s. 4157-75
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/26277108 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20160722 $b ABA008
- 991 __
- $a 20160805120910 $b ABA008
- 999 __
- $a ok $b bmc $g 1155052 $s 944910
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2015 $b 282 $c 21 $d 4157-75 $e 20150911 $i 1742-4658 $m The FEBS journal $n FEBS J $x MED00008414
- LZP __
- $a Pubmed-20160722
