Mitochondrial diseases – it’s not about energy, after all

ITQB/IBET Seminar

Title: Mitochondrial diseases – it’s not about energy, after all

Speaker: Nuno Raimundo

From: Dept. Biochemistry II, Universitatsmedizin Goettingen, Germany

Host: Catarina Brito, Animal Cell Technology Unit

Abstract:

Mitochondrial dysfunction presents as pathology associated with perturbations in redox homeostasis, autophagy, metabolic signaling, and apoptosis. However, the underlying molecular mechanisms and the complex tissue-specificity remain largely obscure. We have unveiled that pathologic activation of AMPK by mitochondrial signaling can trigger E2F1-dependent apoptosis. Interestingly, in a mouse model of mitochondrial malfunction, AMPK activation is observed in most tissues, but E2F1 activation and apoptosis are tissue-specific. Since AMPK is a major regulator of macroautophagy, we hypothesize that the balance between the pathways AMPK→macroautophagy and AMPK→E2F1→apoptosis determines the tissue-specificity of the apoptosis response and consequent disease phenotype. Our data shows that apoptosis occurs in tissues where the AMPK→autophagy axis is outcompeted by the AMPK→E2F1→apoptosis pathway, while the tissues that effectively induce the autophagic signaling are able to avoid apoptosis. These results lay the path for a new strategy to treat mitochondrial pathology by enhancing the autophagic capacity of tissues.

Nuno Raimundo, Short CV
Nuno Raimundo is an AA (Alentejano abroad). After graduating in Biochemistry at FCUL, he worked as a research assistant in redox metabolism. In 2003, NR moved to Finland to start his PhD at the University of Helsinki, studying mitochondrial diseases leading to cancer formation. In 2008 he started his post-doctoral work in the lab of Gerald Shadel at Yale University (New Haven, CT, USA), focusing on the signaling role of mitochondria. The main contribution of NR during his post-doctoral work was the demonstration that mitochondrial malfunction causes disease not due to decreased energy output but to the activation of pathologic signaling pathways. In 2013, NR became a Junior Group Leader at the Georg August University Goettingen (Germany). His research focuses on regulation of cell fate by mitochondria, employing multi-dimensional genomics, advanced imaging and molecular biology approaches.