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{{MitoFit page name}}
{{MitoFit page name}}
{{Publication
{{Publication
|title=Crispim Marcell1, Verdaguer IB, Katzin AM (2019) Effects of atovaquone and 4-nitrobenzoate on ''Plasmodium falciparum'' respiration. MitoFit Preprint Arch  doi:10.26124/mitofit:ea19.MiPSchool.0007.
|title=Crispim M, Verdaguer IB, Zafra CA, Katzin AM (2019) Effects of atovaquone and 4-nitrobenzoate on ''Plasmodium falciparum'' respiration. MitoFit Preprint Arch  [[doi:10.26124/mitofit:ea19.MiPSchool.0007.v2]].
|info=[[File:MitoFit Preprint Arch pdf.png|left|160px|link=http://www.mitofit.org/images/2/24/Di_Marcello_2019_MitoFit_Preprint_Arch_doi_10.26214mitofitea19.MiPSchool.0005.pdf |MitoFit pdf]]  <big><big>'''[http://www.mitofit.org/images/2/24/Di_Marcello_2019_MitoFit_Preprint_Arch_doi_10.26214mitofitea19.MiPSchool.0005.pdf Partitioning between cytochrome c oxidase and alternative oxidase studied by oxygen kinetics of dark respiration in ''Chlamydomonas reinhardtii'': a microalgae model organism]'''</big></big>
|info=[[File:MitoFit Preprint Arch pdf.png|left|160px|link=https://www.mitofit.org/images/6/68/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.v2.pdf |MitoFit pdf]]  <big><big>'''[https://www.mitofit.org/images/6/68/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.v2.pdf Effects of atovaquone and 4-nitrobenzoate on ''Plasmodium falciparum'' respiration]'''</big></big>
|authors=Di Marcello M, Iglesias-Gonzalez J, Meszaros A, Haider M, Gnaiger E, Huete-Ortega M
|authors=Crispim M, Verdaguer IB, Zafra CA, Katzin AM
|year=2019
|year=2019-06-27
|journal=MitoFit Preprint Arch
|journal=MitoFit Preprint Arch
|abstract=Version 1 ('''v1''') '''2019-06-15''' [http://www.mitofit.org/images/0/09/Di_Marcello_2019_MitoFit_Preprint_Arch.pdf doi:10.26124/mitofit:ea19.MiPSchool.0005]
|abstract=>>Versions: ('''v2''') '''2019-06-27''' [https://www.mitofit.org/images/6/68/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.v2.pdf doi:10.26124/mitofit:ea19.MiPSchool.0007.v2]; v1 2019-06-17 [https://wiki.oroboros.at/images/8/81/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.pdf doi:10.26124/mitofit:ea19.MiPSchool.0007]
::: <small>Versions [https://wiki.oroboros.at/images/8/81/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.pdf doi:10.26124/mitofit:ea19.MiPSchool.0007]


Bioenergetics is the study of how living organisms acquire and transform energy to perform biological work. Energetic coupling between chloroplasts and mitochondria has been described in algae, demonstrating the a good functionality and interaction between both organelles is necessary to maintain metabolic integrity. High-resolution respirometry (HRR) is widely used to assess mitochondrial respiration and other bioenergetics parameters in the biomedical field of mitochondrial research and its clinical applications. In our interdisciplinary study, we adapted the multimodal approach of the Oroboros O2k high-resolution respirometer to investigate algal bioenergetics for biotechnological purposes. - ''Extended abstract''
 
|keywords=AOX
== Although atovaquone is one of the newest antimalarial compounds discovered, resistant parasites have already been reported1. Atovaquone mechanism of action is established to be the competition with ubiquinol (UQH2) for the bc1 union at mitochondrial cytochrome bc1 complex and preventing the parasite from maintaining an oxidized ubiquinone (UQ) pool, essential for the DHODH activity and consequently for the pyrimidine's biosynthesis. In this sense, possible inhibitors of the ubiquinone biosynthesis pathway would be candidates by stimulating the effects of atovaquone. 4-nitrobenzoate (4-NB) is a well-known inhibitor of 4HPT (4-hydroxybenzoate polyprenyltransferase), the first enzyme of UQ biosynthesis. 4-NB also showed an important effect on reducing the UQs pool in P. falciparum. Herein is presenting the effect of atovaquone and 4-NB on parasitic respiration UQ biosynthesis. The purpose of this study was to better understand the atovaquone mechanism of action in a molecular scale, drug target potential of UQ biosynthesis. Oxygen consumption assays revealed 4-NB potentiates atovaquone mitochondrial effects and showed itself the ability to decrease the respiration rate. ==
|editor=[[Gnaiger E]] & [[Iglesias-Gonzalez J]],
- ''Extended abstract''
|mipnetlab=AT Innsbruck Oroboros, AT Innsbruck Gnaiger E
|keywords=
|editor=[[Iglesias-Gonzalez J]]
|mipnetlab=
}}
}}
{{NextGen-O2k H2020-support}}
 
== Affiliations ==
== Affiliations ==
Di Marcello M(1), Iglesias-Gonzalez J(1), Meszaros A(1,2), Haider M(3), Gnaiger E(1,2), Huete-Ortega M(1)
Crispim Marcell(1) , Verdaguer IB(1), Zafra CA(1), Katzin AM(1)
::::# Oroboros Instruments, Innsbruck, Austria - marco.dimarcello@oroboros.at
::::# Dept. of Parasitology, Laboratório de Malária, Univ. of Sao Paulo, Sao Paulo, Brazil. Av. Prof. Lineu Prestes, 1374 - Edifício Biomédicas II - Cidade Universitária "Armando Salles Oliveira" - CEP: 05508-000.- marcell@usp.br
::::# D Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Med Univ Innsbruck, Austria
 
::::# SHTech, Innsbruck, Austria


== Results ==
== Results ==
[[File:Di Marcello 2019 MitoFit Preprint Arch EA Figure 1..png]]
[[File:Crispim 2019 MitoFit Preprin Arch EA Figure 1.png|700px]]
[[File:Di Marcello 2019 MitoFit Preprint Arch EA Figure 2.png]]
 
== References ==
== References ==
:::# Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol 1782:31-70. - [[Doerrier 2018 Methods Mol Biol |»Bioblast link«]]
:::# Staines HM, Burrow R, Teo BH, Chis Ster I, Kremsner PG, Krishna S (2018) Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. J Antimicrob Chemother 73(3):581-595.
:::# Young L, Shiba T, Harada S, Kita K, Albury MS, Moore AL (2013) The alternative oxidases: simple oxidoreductase proteins with complex functions. Biochem Soc Trans 41:1305-11. - [[Young 2013 Biochem Soc Trans |»Bioblast link«]]
:::# Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. J Parasitol 91(3):484-6.
:::# [[SUIT-022_O2_ce_D051 |www.bioblast.at/index.php/SUIT-022_O2_ce_D051]]
:::# Tonhosolo R, Gabriel HB, Matsumura HY, Cabral FJ, Yamamoto MM, D’Alexandri FL, Sussmann RAC, Belmonte R, Peres VJ, Crick DC, Wunderlich G, Kimura EA, Katzin AM (2010) Intraerythrocytic stages of Plasmodium falciparum biosynthesize menaquinone. FEBS Lett 584: 4761–4768.
:::# [[SUIT-023_O2_ce_D053 |www.bioblast.at/index.php/SUIT-023_O2_ce_D053]]
:::# Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J. Parasitol 65:  418–20.
:::# Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - [[Gnaiger 2001 Respir Physiol |»Bioblast link«]]
:::# Murphy AD, Doeller JE, Hearn B, Lang-Unnasch N (1997) Plasmodium falciparum: cyanide-resistant oxygen consumption, Exp Parasitol 87: 112–120.  
:::# Meszaros AT, Haider M, Di Marcello M, Gnaiger E (2018) High-resolution mitochondrial oxygen kinetics as diagnostic tool in Complex IV impairments. Abstract Mitochondrial Medicine 2018 Hinxton UK. -  - [[Meszaros_2018_Mt_Med_Hinxton |»Bioblast link«]]
:::# Forsman U, Sjöberg M, Turunen M, Sindelar PJ (2010) 4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures. Nat Chem Biol 6(7):515-7.  
:::# Scandurra FM, Gnaiger E (2010) Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics. Adv Exp Med Biol 662:7-25. - [[Scandurra 2010 Adv Exp Med Biol |»Bioblast link«]]
 
== Event ==
::::» [[MiPschool Coimbra 2019]]
 


== Preprints for [[Gentle Science]] ==
{{MitoFit preprint}}


{{Labeling
{{Labeling
|area=Respiration, Instruments;methods, Comparative MiP;environmental MiP
|area=
|organism=Plants
|organism=
|preparations=Intact cells
|preparations=
|enzymes=Complex IV;cytochrome c oxidase
|enzymes=
|topics=Oxygen kinetics
|topics=
|couplingstates=ROUTINE
|couplingstates=
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Preprints
}}
}}

Revision as of 17:35, 30 November 2020


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Crispim 2019 MitoFit Preprint Arch EA

Publications in the MiPMap
Crispim M, Verdaguer IB, Zafra CA, Katzin AM (2019) Effects of atovaquone and 4-nitrobenzoate on Plasmodium falciparum respiration. MitoFit Preprint Arch doi:10.26124/mitofit:ea19.MiPSchool.0007.v2.

»

MitoFit pdf

Effects of atovaquone and 4-nitrobenzoate on Plasmodium falciparum respiration

Crispim M, Verdaguer IB, Zafra CA, Katzin AM (2019-06-27) MitoFit Preprint Arch

Abstract: >>Versions: (v2) 2019-06-27 doi:10.26124/mitofit:ea19.MiPSchool.0007.v2; v1 2019-06-17 doi:10.26124/mitofit:ea19.MiPSchool.0007

Versions doi:10.26124/mitofit:ea19.MiPSchool.0007


Although atovaquone is one of the newest antimalarial compounds discovered, resistant parasites have already been reported1. Atovaquone mechanism of action is established to be the competition with ubiquinol (UQH2) for the bc1 union at mitochondrial cytochrome bc1 complex and preventing the parasite from maintaining an oxidized ubiquinone (UQ) pool, essential for the DHODH activity and consequently for the pyrimidine's biosynthesis. In this sense, possible inhibitors of the ubiquinone biosynthesis pathway would be candidates by stimulating the effects of atovaquone. 4-nitrobenzoate (4-NB) is a well-known inhibitor of 4HPT (4-hydroxybenzoate polyprenyltransferase), the first enzyme of UQ biosynthesis. 4-NB also showed an important effect on reducing the UQs pool in P. falciparum. Herein is presenting the effect of atovaquone and 4-NB on parasitic respiration UQ biosynthesis. The purpose of this study was to better understand the atovaquone mechanism of action in a molecular scale, drug target potential of UQ biosynthesis. Oxygen consumption assays revealed 4-NB potentiates atovaquone mitochondrial effects and showed itself the ability to decrease the respiration rate.

- Extended abstract

Bioblast editor: Iglesias-Gonzalez J


Affiliations

Crispim Marcell(1) , Verdaguer IB(1), Zafra CA(1), Katzin AM(1)

  1. Dept. of Parasitology, Laboratório de Malária, Univ. of Sao Paulo, Sao Paulo, Brazil. Av. Prof. Lineu Prestes, 1374 - Edifício Biomédicas II - Cidade Universitária "Armando Salles Oliveira" - CEP: 05508-000.- [email protected]


Results

Crispim 2019 MitoFit Preprin Arch EA Figure 1.png

References

  1. Staines HM, Burrow R, Teo BH, Chis Ster I, Kremsner PG, Krishna S (2018) Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. J Antimicrob Chemother 73(3):581-595.
  2. Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. J Parasitol 91(3):484-6.
  3. Tonhosolo R, Gabriel HB, Matsumura HY, Cabral FJ, Yamamoto MM, D’Alexandri FL, Sussmann RAC, Belmonte R, Peres VJ, Crick DC, Wunderlich G, Kimura EA, Katzin AM (2010) Intraerythrocytic stages of Plasmodium falciparum biosynthesize menaquinone. FEBS Lett 584: 4761–4768.
  4. Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J. Parasitol 65: 418–20.
  5. Murphy AD, Doeller JE, Hearn B, Lang-Unnasch N (1997) Plasmodium falciparum: cyanide-resistant oxygen consumption, Exp Parasitol 87: 112–120.
  6. Forsman U, Sjöberg M, Turunen M, Sindelar PJ (2010) 4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures. Nat Chem Biol 6(7):515-7.

Event

» MiPschool Coimbra 2019


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