Seminario de Investigación: Intercellular transfer reconfigures mitochondrial content and function in glioblastoma

Rubén Quintana-Cabrera, Instituto Cajal-CSIC. Madrid

Abstract: The acquisition of mitochondria through intercellular connections or via endocytosis is a biological concept recently shown to promote tumor growth in glioblastoma, the most common and aggressive brain tumor. However, the molecular mechanisms behind those processes are yet to be characterized. Here, we have used a series of genetic and pharmacological approaches to uncover how exogenous organelle importation rewires the native mitochondrial content and function in glioblastoma cells. Capitalizing on connexin-43 (Cx43) as a key modulator of mitochondrial acquisition, we show a differential impact for this protein on the acquisition of isolated or transferred mitochondria from co-cultured fibroblast and primary astrocytes. The importation of exogenous organelles remodels the content, protein composition and native configuration, as well as the functionality of the endogenous mitochondrial network in glioblastoma. In sum, we provide evidences for a functional remodeling of the native mitochondrial network in glioblastoma cells, paving the way to correct alterations in the respiratory metabolism aimed to halt glioblastoma development.


Bio: My work aims to characterize molecular determinants of mitochondrial physiology: redox status, bioenergetics, metabolism, dynamics, ultrastructure and intercellular transfer, to provide novel therapeutic approaches, particularly in the nervous system. At the Univ. Salamanca, (USAL), I contributed relevant publications on mitochondrial and neural redox systems during my European PhD. In the main Quintana-Cabrera et al., Nat.Comm, 2012, we described how γ-glutamylcysteine acts as a mitochondrial antioxidant in neuroprotective gene therapy, worthy of several awards. During my postdoc at the University of Padua (Italy), we contributed seminal works on mitochondrial dynamics and ultrastructure at setting respiratory bioenergetics (Cell, 2013) tissue homeostasis (Cell Metabolism, 2015) and autophagy sorting of mitochondria (Nat.Comm., 2019), among other articles on mitochondrial bioenergetics in cancer and mitochondriopaties. In Quintana-Cabrera et al., Nat.Comm., 2018, we described how cristae engage ATPase oligomerization and activity to prevent mitochondrial dysfunction and cell death after a respiratory blockage. We also linked ultrastructure and ATPase at setting transition pore occurrence and mitochondrial redox status. Back to USAL with a Juan de la Cierva-Incorporación and Marie Curie-IF fellowships, I further contributed to insightful works in neural metabolic and redox communication. Endorsed by my background and awarded for the initial work on it, my current interests as a Ramón y Cajal fellow at the Cajal Institute (CSIC, Madrid) focus on exogenous mitochondrial acquisition and intercellular transfer, aiming to lead a groundbreaking, nascent field to uncover how mitochondrial content and functional reprogramming drive physio(patho)logy.

Fecha y Hora: viernes 2 de diciembre, 12.30 horas

Lugar: Seminario 4