ER/Mitochondria contacts
Mitochondrial Ca2+ waves
3D mitochondrial structure

 

Description

The research activity focuses on the study of the mitochondrial calcium uniporter (MCU), the Ca2+ uptake pathway of mitochondria identified in 2011 by the group. The work includes the investigation of the structure/function relationship of MCU and its regulators, and of the role of MCU in the physiology and pathology of striated muscles, endocrine cells and neurons, both in cell cultures and in LoxP/CRE based transgenic mouse lines in which MCU is specifically ablated in a tissue.

5 recent publications

  • D. De Stefani, A. Raffaello, E. Teardo, I. Szabo, R. Rizzuto (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336-340.
  • R. Rizzuto, D. De Stefani, A. Raffaello, C. Mammucari (2012) Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol. 13:566-78.
  • A. Raffaello, D. De Stefani, D. Sabbadin, E. Teardo, G. Merli, A. Picard, V. Checchetto, S. Moro, I. Szabò, R. Rizzuto (2013) The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J. 32:2362-76.
  • M. Patron V. Checchetto, A. Raffaello, E. Teardo, D. Vecellio Reane, M. Mantoan, V. Granatiero, I. Szabò, D. De Stefani, R. Rizzuto (2014) MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell 53, 726-37.
  • C.V. Logan, G. Szabadkai, I.A. Sharpe, D.A. Parry DA, S. Torelli, ..., R. Rizzuto, UK10K Consortium, M.R. Duchen, F. Muntoni, E. Sheridan (2014) Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling. Nat Genet. 46, 188-93.

 

Grants

  • European Research Council, Ideas Advanced Grant “Mitocalcium” (2012-2016).
  • National Institute of Aging (NIA) Program Project. “A Mitochondrial Longevity Pathway: p66shc Mechanisms” (2013-2018)
  • Italian Minister of Health “Metabolic defects in stem cells as major cause of age” (2013-2015)
  • Ministry of Education – FIRB “From single molecules to the anumal model: an integrated approach to the study of intra- and inter-cellular signals) (2012-2015)
  • Telethon “Therapeutic strategies to combat mitochondrial disorders” (2011-2014)
  • AIRC (Italian Association for Cancer Research) “Molecular basis for triple-negative breast cancer metastasis: new tools for diagnosis and therapy” (2010-2015)
  • Cariplo Foundation “Spinocerebellar ataxia type 28, from molecular pathogenesis to preclinical treatment” (coordinator Giorgio Casari) (2013-2015)
  • Cariparo Foundation “Mitochondrial Ca2+ uptake and cardiac pathophysiology” (coordinator F. Di Lisa) (2013-2015)