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 type: Research Grants - Young Investigators Grants
• Duration: July 01, 2014 - June 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal researcher: Marcos Túlio de Oliveira
• Grantee: Marcos Túlio de Oliveira
• Home Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated 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

(12)

(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)

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. Web of Science Citations: 0.

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. Web of Science Citations: 0.

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. Web of Science Citations: 1.

SAARI, SINA; GARCIA, GEOVANA S.; BREMER, KATHARINA; CHIODA, MARINA M.; ANDJELKOVIC, ANA; DEBES, PAUL V.; NIKINMAA, MIKKO; SZIBOR, MARTEN; DUFOUR, ERIC; RUSTIN, PIERRE; OLIVEIRA, MARCOS T.; JACOBS, HOWARD T. 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. Web of Science Citations: 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. Web of Science Citations: 2.

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. Web of Science Citations: 1.

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. Web of Science Citations: 3.

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. Web of Science Citations: 11.

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. Web of Science Citations: 8.

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. Web of Science Citations: 8.

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. Web of Science Citations: 8.

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. Web of Science Citations: 8.