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Evolution of the cardiolipin biosynthetic pathway: biochemical implications for the evolution of the Eukarya domain

Grant number: 16/12999-0
Support type:Research Grants - Young Investigators Grants
Duration: November 01, 2016 - October 31, 2019
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Luis Alberto Luevano Martinez
Grantee:Luis Alberto Luevano Martinez
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):16/21778-8 - Evolution of the cardiolipin biosynthetic pathway: biochemical implications for the evolution of the Eukarya domain, BP.JP


Cardiolipin (CL) is the main anionic phospholipid found in energy-transducing membranes and is widely distributed throughout all taxonomical levels. This phospholipid provides shape, charge and osmotic support to these membranes due to its biophysical properties. In addition, it provides functionality to the proteins inserted in this membrane. Defects in the biosynthesis or remodeling of cardiolipin have been related to severe diseases such as Barth syndrome. Despite the efforts to understand the physiological importance of this phospholipid little is known about the origin and diversification of the pathway responsible for its synthesis in the Eukarya domain. CL remodeling, or the exchange of saturated acyl chains for unsaturated chains, is found exclusively in this domain. Its physiological significance is still largely unknown and prone to speculations. Different from bacteria, eukaryote need a continuous supply of CL in mitochondria. This dependence results in the co-evolution of most of the protein processes residing in this organelle with this metabolic pathway. In this project, I will dissect the evolution of this pathway by reconstructing, expressing and analyzing the physicochemical and kinetic properties of the ancestral enzymes using techniques from evolutionary biology, biochemistry and molecular biology. Thus, this project also attempts to study the co-evolution of this pathway with the rise and diversification of the mitochondrial anionic carriers (MAC). These proteins play a key role in the communication between mitochondria and its cellular environment. An example of the importance of these proteins in the secondary metabolism is the large quantity of metabolites transported by them. A better understanding of the mechanisms giving rise to this co-dependence will allow understand the success of the endosymbiotic process that subsequently will permit the rise of the Eukarya domain. (AU)

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)
MENEZES-FILHO, SERGIO L.; AMIGO, IGNACIO; LUEVANO-MARTINEZ, LUIS ALBERTO; KOWALTOWSKI, ALICIA J. Fasting promotes functional changes in liver mitochondria. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, v. 1860, n. 2, p. 129-135, FEB 1 2019. Web of Science Citations: 0.
LUEVANO-MARTINEZ, LUIS ALBERTO; CALDEIRA DA SILVA, CAMILLE C.; NICASTRO, GIANLUCCA G.; SCHUMACHER, I, ROBERT; KOWALTOWSKI, ALICIA J.; GOMES, SUELY L. Mitochondrial alternative oxidase is determinant for growth and sporulation in the early diverging fungus Blastocladiella emersonii. FUNGAL BIOLOGY, v. 123, n. 1, p. 59-65, JAN 2019. Web of Science Citations: 0.
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. Web of Science Citations: 0.

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