c/o Complesso Biologico Interdipartimentale
Viale Giuseppe Colombo 3
I have mainly contributed to the study of the role played by the physical/functional connection between endoplasmic reticulum (ER) and mitochondria in the regulation of key intracellular processes, such as the modulation of cell death and cell bioenergetics. In particular, ER-mitochondria interplay has been investigated in the context of Familial Alzheimer’s disease.
My research focused on the exploration of the molecular nature and of the relationship between proteins mediating ER-mitochondria tethering. I’m currently interested in the generation of novel tools to study organelles’ juxtaposition in living cells, as well as to investigate the mechanisms leading to the generation and deciphering of Ca2+ microdomains in localized subcellular compartments. In addition, by employing and creating specific genetically-encoded fluorescent probes, I’m investigating the dynamics (particularly within mitochondria) of different metabolites and signalling molecules (Ca2+, ATP, pyruvate, lactate, etc.), both in cell physiology and pathology.
The final goal of my research activity is to understand whether alterations in these pathways are linked to the onset and progression of human pathologies, as well as to test their potential as possible therapeutic targets or as disease biomarkers.
Hedskog L, Pinho CM, Filadi R, Rönnbäck A, Hertwig L, Wiehager B, Larssen P, Gellhaar S, Sandebring A, Westerlund M, Graff C, Winblad B, Galter D, Behbahani H, Pizzo P, Glaser E, Ankarcrona M. (2013). Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models. Proc Natl Acad Sci U S A. 110(19):7916-21.
Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P. (2015). Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci U S A. 112(17):E2174-81.
Filadi R, Greotti E, Turacchio G, Luini, A, Pozzan T, Pizzo P. (2016). Presenilin 2 modulates endoplasmic reticulum-mitochondria coupling by tuning the antagonistic effect of mitofusin 2. Cell Reports,15(10):2226-38.
Filadi R, Leal NS, Schreiner B, Rossi A, Dentoni G, Pinho CM, Wiehager B, Cieri D, Calì T, Pizzo P, Ankarcrona M. (2018). TOM70 Sustains Cell Bioenergetics by Promoting IP3R3-Mediated ER to Mitochondria Ca2+ Transfer. Curr Biol. 28(3):369-382.
Fedeli C.*, Filadi R.*, Rossi A., Mammucari C. and Pizzo P. (2019). PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca2+ homeostasis. Autophagy. 20:1-19.