title: Calcium and magnesium ions modulate the oligomeric state and function of mitochondrial 2-Cys peroxiredoxins inLeishmaniaparasites.
abstract: Leishmaniaparasites have evolved a number of strategies to cope with the harsh environmental changes during mammalian infection. One of these mechanisms involves the functional gain that allows mitochondrial 2-Cys peroxiredoxins to act as molecular chaperones when forming decamers. This function is critical for parasite infectivity in mammals, and its activation has been considered to be controlled exclusively by the enzyme redox state under physiological conditions. Herein, we have revealed that magnesium and calcium ions play a major role in modulating the ability of these enzymes to act as molecular chaperones, surpassing the redox effect. These ions are directly involved in mitochondrial metabolism and participate in a novel mechanism to stabilize the decameric form of 2-Cys peroxiredoxins inLeishmaniamitochondria. Moreover, we have demonstrated that a constitutively dimeric Prx1m mutant impairs the survival ofLeishmaniaunder heat stress, supporting the central role of the chaperone function of Prx1m forLeishmaniaparasites during the transition from insect to mammalian hosts.
authors.affiliation: From the Biosciences National Laboratory, National Center for Research in Energy and Materials, Rua Giuseppe Maximo Scolfaro 10000, 13083-100 Campinas/SP, Brazil.
authors.forename: Mariana A B
authors.initials: MAB
authors.lastname: Morais
authors.affiliation: From the Biosciences National Laboratory, National Center for Research in Energy and Materials, Rua Giuseppe Maximo Scolfaro 10000, 13083-100 Campinas/SP, Brazil.
authors.forename: Priscila O
authors.initials: PO
authors.lastname: Giuseppe
authors.affiliation: the Proteomics and Protein Engineering Laboratory, Carlos Chagas Institute, Fiocruz, Rua Professor Algacyr Munhoz Mader 2135, 81310-020 Curitiba/PR, Brazil.
authors.forename: Tatiana A C B
authors.initials: TACB
authors.lastname: Souza
authors.affiliation: the i3S-Institute for Investigation and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.|the Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Castro
authors.affiliation: From the Biosciences National Laboratory, National Center for Research in Energy and Materials, Rua Giuseppe Maximo Scolfaro 10000, 13083-100 Campinas/SP, Brazil.
authors.forename: Rodrigo V
authors.initials: RV
authors.lastname: Honorato
authors.affiliation: From the Biosciences National Laboratory, National Center for Research in Energy and Materials, Rua Giuseppe Maximo Scolfaro 10000, 13083-100 Campinas/SP, Brazil.
authors.forename: Paulo S L
authors.initials: PSL
authors.lastname: Oliveira
authors.affiliation: the Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of the State of São Paulo, Rua do Matão 14, 05508-090 São Paulo/SP, Brazil, and.
authors.forename: Luis E S
authors.initials: LES
authors.lastname: Netto
authors.affiliation: the i3S-Institute for Investigation and Innovation in Health, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.|the Institute of Molecular and Cell Biology (IBMC), University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal.|the Abel Salazar Biomedical Sciences Institute, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Tomas
authors.affiliation: From the Biosciences National Laboratory, National Center for Research in Energy and Materials, Rua Giuseppe Maximo Scolfaro 10000, 13083-100 Campinas/SP, Brazil, mario.murakami@lnbio.cnpem.br.
authors.forename: Mario T
authors.identifier: 0000-0002-0405-8010
authors.initials: MT
authors.lastname: Murakami
mesh_terms: D016880:Anisotropy; D002118:Calcium / Q000378:metabolism*; D002845:Chromatography; D004220:Disulfides / Q000737:chemistry; D005470:Fluorometry; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007891:Leishmania / Q000378:metabolism*; D008027:Light; D008274:Magnesium / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D054464:Peroxiredoxins / Q000378:metabolism*; D055503:Protein Multimerization; D015800:Protozoan Proteins / Q000378:metabolism*; D012542:Scattering, Radiation; D013696:Temperature
chemical_list: D004220:Disulfides; D018398:Homeodomain Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C512693:PRRX2 protein, human; D015800:Protozoan Proteins; C504194:2-cys peroxiredoxin, human; D054464:Peroxiredoxins; D008274:Magnesium; D010100:Oxygen; D002118:Calcium
keywords: Leishmania; calcium; molecular chaperone; oligomerization; peroxiredoxin