Investigating the metabolic alterations caused by the transgenic expression of the mitochondrial alternative oxidase of Ciona intestinalis in Drosophila melanogaster

• Grant number: 14/02253-6
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: July 01, 2014
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marcos Túlio de Oliveira
• Grantee: Marcos Túlio de Oliveira
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• City of the host institution: Jaboticabal
• Associated research grant(s): 21/06711-2 - Modulation of tissue growth and biomass accumulation by the mitochondrial alternative oxidase, AP.JP2
• Associated scholarship(s): 17/17645-5 - Tissue-specific expression of alternative oxidase in Drosophila melanogaster, BP.IC; 17/13743-2 - Alternative enzymes and molecular evolution of mitochondrial respiratory chain genes of Ciona intestinalis (Tunicata: Ascidiacea), BP.IC; 17/03806-7 - Evaluation of the thermogenic properties of the mitochondrial alternative oxidase expressed in Drosophila melanogaster, BP.MS; + associated scholarships 17/02813-0 - Mitochondrial proteomics of Drosophila melanogaster expressing the alternative oxidase under different dietary conditions, BP.MS; 16/00013-3 - Temperature variation effects on AOX flies development, BP.IC; 15/14547-7 - Effects of AOX expression in mitochondrial DNA helicase mutants of Drosophila melanogaster, BP.MS; 15/02174-1 - Carbohydrate restriction effect on AOX flies development, BP.IC - associated scholarships

Abstract

The respiratory chain alternative enzymes constitute additional pathways to the mitochondrial oxidative phosphorylation (OXPHOS) system, in which oxygen consumption is uncoupled from ATP production. The expression of alternative oxidases and alternative NADH dehydrogenases from tunicates and fungi in the fruit fly Drosophila melanogaster, in the mouse and in cultured human cells has proven to be benign and to counteract deleterious effects of defective OXPHOS systems, such as the high production of reactive oxygen species. The observed benefits are in paradox with the fact that genes for alternative enzymes were lost independently, early in the evolution of Vertebrata and Arthropoda. We thus propose to investigate the functions of an alternative enzyme from Ciona intestinalis (Tunicata: Ascidiacea), the alternative oxidase (AOX), when expressed in transgenic fruitflies. These organisms will be challenged by thermal and dietetic stress conditions to study mitochondrial metabolism and to evaluate aerobic performance. We will use a variety of molecular biology techniques (including RNA-Seq and high resolution mass spectrometry) to investigate the changes in cell transcriptomics and mitochondrial proteomics, providing data about the physiological alterations caused by AOX and insights into the evolution of the mitochondrial alternative pathways in animals. (AU)

Scientific publications

(23)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SAARI, SINA; GARCIA, GEOVANA S.; BREMER, KATHARINA; CHIODA, MARINA M.; ANDJELKOVIC, ANA; DEBES, PAUL V.; NIKINMAA, MIKKO; SZIBOR, MARTEN; DUFOUR, ERIC; RUSTIN, PIERRE; et al. Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1865, n. 4, SI, p. 854-866, APR 1 2019. (15/02174-1, 14/02253-6, 16/00013-3)

OLIVEIRA, MARCOS T.; PONTES, CAROLINA DE BOVI; CIESIELSKI, GRZEGORZ L.. Roles of the mitochondrial replisome in mitochondrial DNA deletion formation. GENETICS AND MOLECULAR BIOLOGY, v. 43, n. 1, 1, 2020. (17/04372-0, 14/02253-6)

KAGUNI, LAURIE S.; OLIVEIRA, MARCOS T.. Structure, function and evolution of the animal mitochondrial replicative DNA helicase. CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, v. 51, n. 1, p. 53-64, JAN 2 2016. (14/02253-6)

ALVES BATISTA, DIEGO FELIPE; FREITAS NETO, OLIVEIRO CAETANO; BARROW, PAUL ANDREW; DE OLIVEIRA, MARCOS TULIO; ALMEIDA, ADRIANA MARIA; FERRAUDO, ANTONIO SERGIO; BERCHIERI, JR., ANGELO. Identification and characterization of regions of difference between the Salmonella Gallinarum biovar Gallinarum and the Salmonella Gallinarum biovar Pullorum genomes. INFECTION GENETICS AND EVOLUTION, v. 30, p. 74-81, MAR 2015. (11/23483-1, 14/02253-6)

SALMINEN, TIINA S.; OLIVEIRA, MARCOS T.; CANNINO, GIUSEPPE; LILLSUNDE, PAIVI; JACOBS, HOWARD T.; KAGUNI, LAURIE S.. Mitochondrial genotype modulates mtDNA copy number and organismal phenotype in Drosophila. MITOCHONDRION, v. 34, p. 75-83, MAY 2017. (14/02253-6)

OLIVEIRA, MARCOS T.; HAUKKA, JANI; KAGUNI, LAURIE S.. Evolution of the Metazoan Mitochondrial Replicase. GENOME BIOLOGY AND EVOLUTION, v. 7, n. 4, p. 943-959, APR 2015. (14/02253-6)

URBINATI, ISMAEL; STAFUZZA, NEDENIA BONVINO; OLIVEIRA, MARCOS TULIO; SELEGUIM CHUD, TATIANE CRISTINA; HIGA, ROBERTO HIROSHI; DE ALMEIDA REGITANO, LUCIANA CORREIA; DE ALENCAR, MAURICIO MELLO; BUZANSKAS, MARCOS ELI; MUNARI, DANISIO PRADO. Selection signatures in Canchim beef cattle. JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, v. 7, p. 9-pg., 2016-05-05. (14/02253-6, 13/09050-0, 15/08939-0, 13/19335-2)

OTHONICAR, MURILO F.; GARCIA, GEOVANA S.; OLIVEIRA, MARCOS T.. The alternative enzymes-bearing tunicates lack multiple widely distributed genes coding for peripheral OXPHOS subunits. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1865, n. 3, p. 14-pg., 2024-04-22. (21/06711-2, 17/04372-0, 22/01509-3, 14/02253-6)

OLIVEIRA, MARCOS T.; ANHEZINI, LUCAS; ARAUJO, HELENA M.; OLIVEIRA, MARCUS F.; COUTO-LIMA, CARLOS A.. Boosting life sciences research in Brazil: building a case for a local Drosophila stock center. GENETICS AND MOLECULAR BIOLOGY, v. 47, n. 1, p. 11-pg., 2024-01-01. (17/04372-0, 21/06711-2, 14/02253-6, 22/05632-4)

OLIVEIRA, MARCOS T.; PONTES, CAROLINA DE BOVI; CIESIELSKI, GRZEGORZ L.. Roles of the mitochondrial replisome in mitochondrial DNA deletion formation. GENETICS AND MOLECULAR BIOLOGY, v. 43, n. 1, p. 16-pg., 2020-01-01. (14/02253-6, 17/04372-0)

GARCIA, GEOVANA; OLIVEIRA, MARCOS. Alternative Oxidase Confers Thermogenesis and Increased Growth to Drosophila Larvae under Severe Cold Stress. FASEB JOURNAL, v. 35, p. 2-pg., 2021-05-01. (17/04372-0, 14/02253-6)

CAMARGO, ANDRE F.; CHIODA, MARINA M.; RODRIGUES, ANA P. C.; GARCIA, GEOVANA S.; MCKINNEY, EMILY A.; JACOBS, HOWARD T.; OLIVEIRA, MARCOS T.. Xenotopic expression of alternative electron transport enzymes in animal mitochondria and their impact in health and disease. Cell Biology International, v. 42, n. 6, p. 6-pg., 2018-06-01. (17/03806-7, 14/02253-6, 17/02813-0, 15/14547-7)

CAMARGO, ANDRE F.; CHIODA, MARINA M.; RODRIGUES, ANA P. C.; GARCIA, GEOVANA S.; MCKINNEY, EMILY A.; JACOBS, HOWARD T.; OLIVEIRA, MARCOS T.. Xenotopic expression of alternative electron transport enzymes in animal mitochondria and their impact in health and disease. Cell Biology International, v. 42, n. 6, SI, p. 664-669, JUN 2018. (14/02253-6, 17/03806-7, 17/02813-0, 15/14547-7)

URBINATI, ISMAEL; STAFUZZA, NEDENIA BONVINO; OLIVEIRA, MARCOS TULIO; SELEGUIM CHUD, TATIANE CRISTINA; HIGA, ROBERTO HIROSHI; DE ALMEIDA REGITANO, LUCIANA CORREIA; DE ALENCAR, MAURICIO MELLO; BUZANSKAS, MARCOS ELI; MUNARI, DANISIO PRADO. Selection signatures in Canchim beef cattle. JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, v. 7, MAY 5 2016. (13/09050-0, 13/19335-2, 14/02253-6, 15/08939-0)

MARCOS T. OLIVEIRA; LUCAS ANHEZINI; HELENA M. ARAUJO; MARCUS F. OLIVEIRA; CARLOS A. COUTO-LIMA. Boosting life sciences research in Brazil: building a case for a local Drosophila stock center. GENETICS AND MOLECULAR BIOLOGY, v. 47, n. 1, 2024-02-19. (17/04372-0, 21/06711-2, 22/05632-4, 14/02253-6)

SAARI, SINA; ANDJELKOVIC, ANA; GARCIA, GEOVANA S.; JACOBS, HOWARD T.; OLIVEIRA, MARCOS T.. Expression of Ciona intestinalis AOX causes male reproductive defects in Drosophila melanogaster. BMC Developmental Biology, v. 17, JUL 3 2017. (14/02253-6)

RODRIGUES, ANA PAULA C.; CAMARGO, ANDRE F.; ANDJELKOVIC, ANA; JACOBS, HOWARD T.; OLIVEIRA, MARCOS T.. Developmental arrest in Drosophila melanogaster caused by mitochondrial DNA replication defects cannot be rescued by the alternative oxidase. SCIENTIFIC REPORTS, v. 8, JUL 18 2018. (15/14547-7, 14/02253-6)

SALMINEN, TIINA S.; CANNINO, GIUSEPPE; OLIVEIRA, MARCOS T.; LILLSUNDE, PAIVI; JACOBS, HOWARD T.; KAGUNI, LAURIE S.. Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster. G3-GENES, GENOMES, GENETICS, v. 9, n. 7, p. 2225-2234, JUL 2019. (14/02253-6)

RODRIGUES, ANA PAULA; GOFFART, STEFFI; OLIVEIRA, MARCOS. Distinct Roles of the Mitochondrial DNA Helicase Twinkle in Drosophila Neurons and Muscles. FASEB JOURNAL, v. 35, p. 1-pg., 2021-05-01. (14/02253-6, 17/04372-0)

OLIVEIRA, MARCOS; CAMARGO, ANDRE; GARCIA, GEOVANA; OTHONICAR, MURILO; SAARI, SINA; MARTINS, AILTON; CHIODA, MARINA; JACOBS, HOWARD; DUFOUR, ERIC. Effects of Diet on the Developmental Metabolism of Drosophila Expressing the Ciona intestinalis Alternative Oxidase. FASEB JOURNAL, v. 35, p. 2-pg., 2021-05-01. (14/02253-6, 17/04372-0)

GARCIA, GEOVANA S.; OTHONICAR, MURILO F.; OLIVEIRA, MARCOS T.; COUTO-LIMA, CARLOS A.. An Affordable and Efficient ``Homemade{''} Platform for Drosophila Behavioral Studies, and an Accompanying Protocol for Larval Mitochondrial Respirometry. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 175, SEP 2021. (14/02253-6, 17/04372-0)

SAARI, SINA; GARCIA, GEOVANA S.; BREMER, KATHARINA; CHIODA, MARINA M.; ANDJELKOVIC, ANA; DEBES, PAUL V.; NIKINMAA, MIKKO; SZIBOR, MARTEN; DUFOUR, ERIC; RUSTIN, PIERRE; et al. Alternative respiratory chain enzymes: Therapeutic potential and possible pitfalls. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1865, n. 4, p. 13-pg., 2019-04-01. (14/02253-6, 16/00013-3, 15/02174-1)

SAARI, SINA; KEMPPAINEN, ESKO; TUOMELA, TEA; OLIVEIRA, MARCOS T.; DUFOUR, ERIC; JACOBS, HOWARD T.. Alternative oxidase confers nutritional limitation on Drosophila development. OURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOG, v. 331, n. 6, p. 16-pg., 2019-07-01. (14/02253-6)