Evaluation of the adaptive response of mitochondrial membranes to stress: role of cardiolipin in membrane plasticity, dynamics and pathological situations

• Grant number: 13/04919-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2013
• End date: August 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Luis Alberto Luevano Martinez
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Phospholipids are key players in the formation of membranes and in the first response to stressful situations, by transducing signals at several levels. Because of the importance of them in these kinds of responses, biosynthesis is a finely regulated process. Genetic and biochemical regulation in the biosynthesis of zwitterionic and neutral lipids has been well studied. However, little is known about the cellular signals which regulate anionic phospholipids because their biosynthesis is restricted to mitochondria. Cardiolipin is the main anionic phospholipid found in energy-transducing membranes and is widely distributed throughout all taxonomical levels. In mitochondria, it is found in the inner membrane and provides shape, charge and osmotic support to these membranes due to its biophysical properties. In addition, it helps form respiratory supercomplexes and provides functionality to mitochondrial proteins inserted in this membrane. Defects in the biosynthesis or remodeling of cardiolipin have been related to severe diseases such as Barth syndrome. Previously, we found that cardiolipin biosynthesis is indirectly regulated by inositol. In this project, we attempt to fully dissect mechanisms influencing the biosynthesis of cardiolipin, such as cytosolic and mitochondrial signals, and to describe the biological role of these phospholipids during environmental stress situations. (AU)

Scientific publications

(9)

(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)

AMIGO, IGNACIO; DA CUNHA, FERNANDA M.; FORNI, MARIA FERNANDA; GARCIA-NETO, WILSON; KAKIMOTO, PAMELA A.; LUEVANO-MARTINEZ, LUIS A.; MACEDO, FELIPE; MENEZES-FILHO, SERGIO L.; PELOGGIA, JULIA; KOWALTOWSKI, ALICIA J.. Mitochondrial form, function and signalling in aging. Biochemical Journal, v. 473, n. 20, p. 3421-3449, OCT 2016. (15/15526-3, 10/51906-1, 14/17270-3, 13/04919-9, 15/25776-7, 13/07937-8)

CABRERA-OREFICE, ALFREDO; IBARRA-GARCIA-PADILLA, RODRIGO; MALDONADO-GUZMAN, ROCIO; GUERRERO-CASTILLO, SERGIO; LUEVANO-MARTINEZ, LUIS A.; PEREZ-VAZQUEZ, VICTORIANO; GUTIERREZ-AGUILAR, MANUEL; URIBE-CARVAJAL, SALVADOR. The Saccharomyces cerevisiae mitochondrial unselective channel behaves as a physiological uncoupling system regulated by Ca2+, Mg2+, phosphate and ATP. Journal of Bioenergetics and Biomembranes, v. 47, n. 6, p. 477-491, DEC 2015. (13/04919-9)

LUEVANO-MARTINEZ, LUIS ALBERTO; FORNI, MARIA FERNANDA; DOS SANTOS, VALQUIRIA TIAGO; SOUZA-PINTO, NADJA C.; KOWALTOWSKI, ALICIA J.. Cardiolipin is a key determinant for mtDNA stability and segregation during mitochondrial stress. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1847, n. 6-7, p. 587-598, JUN-JUL 2015. (10/51906-1, 10/18254-0, 13/04919-9, 13/04871-6, 13/07937-8)

LUEVANO-MARTINEZ, LUIS ALBERTO. The chimeric origin of the cardiolipin biosynthetic pathway in the Eukarya domain. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1847, n. 6-7, p. 599-606, JUN-JUL 2015. (13/04919-9)

LUEVANO-MARTINEZ, LUIS ALBERTO; KOWALTOWSKI, ALICIA J.. Topological characterization of the mitochondrial phospholipid scramblase 3. FEBS Letters, v. 591, n. 24, p. 4056-4066, DEC 2017. (16/12999-0, 13/04919-9, 13/07937-8)

AMIGO, IGNACIO; DA CUNHA, FERNANDA M.; FORNI, MARIA FERNANDA; GARCIA-NETO, WILSON; KAKIMOTO, PAMELA A.; LUEVANO-MARTINEZ, LUIS A.; MACEDO, FELIPE; MENEZES-FILHO, SERGIO L.; PELOGGIA, JULIA; KOWALTOWSKI, ALICIA J.. Mitochondrial form, function and signalling in aging. Biochemical Journal, v. 473, p. 29-pg., 2016-10-01. (13/07937-8, 13/04919-9, 15/15526-3, 14/17270-3, 10/51906-1, 15/25776-7)

LUEVANO-MARTINEZ, LUIS ALBERTO; FORNI, MARIA FERNANDA; PELOGGIA, JULIA; WATANABE, II-SEI; KOWALTOWSKI, ALICIA J.. Calorie restriction promotes cardiolipin biosynthesis and distribution between mitochondrial membranes. MECHANISMS OF AGEING AND DEVELOPMENT, v. 162, p. 9-17, MAR 2017. (13/07937-8, 13/04871-6, 13/04919-9)

LUEVANO-MARTINEZ, LUIS ALBERTO; KOWALTOWSKI, ALICIA J.. Phosphatidylglycerol-derived phospholipids have a universal, domain-crossing role in stress responses. Archives of Biochemistry and Biophysics, v. 585, p. 90-97, NOV 1 2015. (13/04919-9, 13/07937-8)

GARCIA-NETO, WILSON; CABRERA-OREFICE, ALFREDO; URIBE-CARVAJAL, SALVADOR; KOWALTOWSKI, ALICIA J.; LUEVANO-MARTINEZ, LUIS ALBERTO. High Osmolarity Environments Activate the Mitochondrial Alternative Oxidase in Debaryomyces Hansenii. PLoS One, v. 12, n. 1, JAN 6 2017. (13/04919-9)