Effects of AOX expression in mitochondrial DNA helicase mutants of Drosophila melanogaster

• Grant number: 15/14547-7
• Support type: Scholarships in Brazil - Master
• Effective date (Start): August 01, 2015
• Effective date (End): July 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Marcos Túlio de Oliveira
• Grantee: Ana Paula Campos Rodrigues
• Home Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil
• Associated research grant: 14/02253-6 - Investigating the metabolic alterations caused by the transgenic expression of the mitochondrial alternative oxidase of Ciona intestinalis in Drosophila melanogaster, AP.JP

Abstract

Mutations in the human gene C10orf2, which encodes for the mitochondrial DNA (mtDNA) helicase, are associated with several cases of mitochondrial and neurodegenerative diseases, such as Progressive External Ophthalmoplegia (PEO), Perrault Syndrome, Infantile-Onset Spinocerebellar Ataxia (IOSCA), among others. The mtDNA helicase, also known as Twinkle, is an enzyme capable of utilizing ATP to translocate along single-stranded DNA and promote unwinding of the double-stranded DNA template during the replication process of this genome. Three mutations analogues to the ones found in the human gene (K388A, W441C e A442P) were modeled in Drosophila melanogaster, causing mtDNA replication problems, reduced respiratory chain activity, and developmental disturbances. The transgenic expression of the mitochondrial alternative oxidase (AOX) from Ciona intestinalis in D. melanogaster has proven to be effective against genetic defects caused by mitochondrial dysfunctions, which in turn can be caused by mtDNA replication problems. The goal of this project is to investigate if the expression of AOX could also alleviate or neutralize the negative effects on fly development caused by mutations in the mtDNA helicase. The appointed Master student will analyze phenotypic data such as larval/pupal viability, biochemical data such as the activity of the respiratory chain complexes, and molecular data such as mtDNA copy number. The results may help understanding the roles of AOX in buffering mitochondrial functions, in addition to help promoting treatment strategies for diseases whose molecular basis are involved with mtDNA replication.

Scientific publications

(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)

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.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

RODRIGUES, Ana Paula Campos. Efeitos da expressão da oxidase alternativa em mutantes da helicase mitocondrial de Drosophila melanogaster. 2017. 72 f. Master's Dissertation - Universidade Estadual Paulista "Júlio de Mesquita Filho" Instituto de Biociências, Letras e Ciências Exatas..