Cardiolipin in neurodegenerative diseases: characterization of oxidized products and modified proteins in a model of Amyotrophic Lateral Sclerosis

• Grant number: 14/11556-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2014
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Sayuri Miyamoto
• Grantee: Isabella Fernanda Dantas Pinto
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Cardiolipin is the principal glycerophospholipid found in the inner mitochondrial membrane and plays an important role in the structure and function of this organelle. The oxidation of cardiolipin is related to activation of cellular apoptosis, development and progression of many pathological processes. Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurodegenerative disease characterized by motor neuron death, is also related to mitochondrial dysfunction; however, the role of cardiolipin in this process has not been clarified yet. Thus, the present study will (I) make a global analysis of ALS brain lipid profile, (II) analyze changes in the composition in fatty acid profile of cardiolipin and their oxidation products in isolated mitochondria, and (III) characterize structural modifications in cytochrome c derived from its interaction with cardiolipin hydroperoxides. As a study model, we will use cultured neuroblastoma cells SH- SY5Y and other tissues of transgenic rats with G93A mutation for ALS For the characterization of lipid and protein fractions, the project will use highly sensitive and specific techniques for the detection and quantification, such as, LC-MS/MS. Thus, with this project we expect to clarify whether there are changes in cardiolipin and total phospholipids profile and their oxidized products in the mitochondria, and also to identify possible biological implication of these changes in the development and progression of neurodegenerative diseases. (AU)

Scientific publications

(4)

(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)

MENEZES-FILHO, SERGIO L.; AMIGO, IGNACIO; PRADO, FERNANDA M.; FERREIRA, NATALIE C.; KOIKE, MARCIA K.; PINTO, ISABELLA F. D.; MIYAMOTO, SAYURI; MONTERO, EDNA F. S.; MEDEIROS, MARISA H. G.; KOWALTOWSKI, ALICIA J.. Caloric restriction protects livers from ischemia/reperfusion damage by preventing Ca2+- induced mitochondrial permeability transition. Free Radical Biology and Medicine, v. 110, p. 219-227, SEP 2017. (12/50500-7, 13/07937-8, 14/11556-2)

QUEIROZ, ADRIANO; DANTAS PINTO, ISABELLA FERNANDA; LIMA, MARICELIA; GIOVANETTI, MARTA; DE JESUS, JAQUELINE GOES; XAVIER, JOILSON; BARRETO, FERNANDA KHOURI; BAPTISTA CANUTO, GISELE ANDRE; DO AMARAL, HELINEIDE RAMOS; BISPO DE FILIPPIS, ANA MARIA; et al. Lipidomic Analysis Reveals Serum Alteration of Plasmalogens in Patients Infected With ZIKA Virus. FRONTIERS IN MICROBIOLOGY, v. 10, APR 12 2019. (13/07937-8, 14/11556-2)

LUEVANO-MARTINEZ, LUIS ALBERTO; PINTO, ISABELLA FERNANDA DANTAS; YOSHINAGA, MARCOS YUKIO; MIYAMOTO, SAYURI. In yeast, cardiolipin unsaturation level plays a key role in mitochondrial function and inner membrane integrity. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1863, n. 7, p. 10-pg., 2022-07-02. (16/12999-0, 14/11556-2, 13/07937-8)

DANTAS PINTO, ISABELLA FERNANDA; CHAVES-FILHO, ADRIANO DE BRITTO; DA CUNHA, DANIELA; MIYAMOTO, SAYURI. Cytochrome c modification and oligomerization induced by cardiolipin hydroperoxides in a membrane mimetic model. Archives of Biochemistry and Biophysics, v. 693, OCT 30 2020. (13/07937-8, 14/11556-2)

Academic Publications

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

PINTO, Isabella Fernanda Dantas. Exploring the role of lipids in protein modification and amyotrophic lateral sclerosis. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.