Characterization of the impact of mitochondria in the metabolism of osteosarcoma cells

• Grant number: 24/10105-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Mariana Camargo Maschietto
• Grantee: Larissa Mariano
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated research grant: 21/06782-7 - Striking the evolutionary process of bone tumors, AP.JP2

Abstract

The mitochondrial involvement in the tumor cell transformation is reflected by Warburg and Crabtree effects, in which there is a preference for glycolysis instead of oxidative phosphorylation, even in the presence of oxygen or high levels of glucose, respectively, at the expense of reduced ATP production. Preliminary experiments, not yet validated, suggest that primary osteosarcoma cells have increased citrate synthase activity, which is an indirect measure of higher mitochondrial mass. In association, this cell showed higher oxygen consumption, higher cell proliferation and higher reactive oxygen species. We hypothesize that a higher biomass increases proportionally the amount of ATP, potentially resulting in the prevalence of Warburg and Crabtree effects. Assuming that highly aggressive tumors, such as osteosarcoma, can acquire mitochondria from other types of cells, a cellular model is being built to study this phenomenon through confocal microscopy. This study will involve the modification of non-tumor fibroblast cell lines through lentiviral transduction to mark their mitochondria. Simultaneously, osteosarcoma cell lines will be transformed to mark alpha-actin, in order to enable the investigation of mitochondrial transference from fibroblasts to osteosarcoma cells. However, the mitochondrial feedback is limited and the association between mitochondrial dynamics and their functional implications in high-risk tumors is not well elucidated. This proposal will characterize the support given by mitochondria to tumor cells, using osteosarcoma as a study model.