Description

Mitochondria STED microscopy

Our research activity is mainly focused on calcium signaling and mitochondrial ion channels. In 2011, we identified the Mitochondrial Calcium Uniporter (MCU), and in 2019 we identified the mitochondrial ATP-sensitive potassium channel (mitoKATP). We study the structure/function relationship of these channels and their role in health and disease. We combine biochemical, cell-based and in vivo approaches to understand their contribution to the physiopathology of different tissues, including skeletal muscle, heart and brain.

Selected publications

• Paggio A, Checchetto V, Campo A, Menabò R, Di Marco G, Di Lisa F, Szabo I, Rizzuto R, De Stefani D. Identification of an ATP-sensitive potassium channel in mitochondria. Nature. 2019 Aug;572(7771):609-613. doi: 10.1038/s41586-019-1498-3. Epub 2019 Aug 21. PubMed PMID: 31435016; PubMed Central PMCID: PMC6726485.
• Gherardi G, Nogara L, Ciciliot S, Fadini GP, Blaauw B, Braghetta P, Bonaldo P, De Stefani D, Rizzuto R, Mammucari C. Loss of mitochondrial calcium uniporter rewires skeletal muscle metabolism and substrate preference. Cell Death Differ. 2019 Jan;26(2):362-381. doi: 10.1038/s41418-018-0191-7. Epub 2018 Sep 19. PubMed PMID: 30232375; PubMed Central PMCID: PMC6329801.
• Patron M, Granatiero V, Espino J, Rizzuto R, De Stefani D. MICU3 is a tissue-specific enhancer of mitochondrial calcium uptake. Cell Death Differ. 2019 Jan;26(1):179-195. doi: 10.1038/s41418-018-0113-8. Epub 2018 May 3. PubMed PMID: 29725115; PubMed Central PMCID: PMC6124646.
• Vecellio Reane D, Vallese F, Checchetto V, Acquasaliente L, Butera G, De Filippis V, Szabò I, Zanotti G, Rizzuto R, Raffaello A. A MICU1 Splice Variant Confers High Sensitivity to the Mitochondrial Ca(2+) Uptake Machinery of Skeletal Muscle. Mol Cell. 2016 Nov 17;64(4):760-773. doi: 10.1016/j.molcel.2016.10.001. Epub 2016 Nov 3. PubMed PMID: 27818145.
• Tosatto A, Sommaggio R, Kummerow C, Bentham RB, Blacker TS, Berecz T, Duchen MR, Rosato A, Bogeski I, Szabadkai G, Rizzuto R, Mammucari C. The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1α. EMBO Mol Med. 2016 May 2;8(5):569-85. doi: 10.15252/emmm.201606255. Print 2016 May. PubMed PMID: 27138568; PubMed Central PMCID: PMC4864890.
• Mammucari C, Gherardi G, Zamparo I, Raffaello A, Boncompagni S, Chemello F, Cagnin S, Braga A, Zanin S, Pallafacchina G, Zentilin L, Sandri M, De Stefani D, Protasi F, Lanfranchi G, Rizzuto R. The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo. Cell Rep. 2015 Mar 3;10(8):1269-79. doi: 10.1016/j.celrep.2015.01.056. Epub 2015 Feb 26. PubMed PMID: 25732818; PubMed Central PMCID: PMC4351162.
• Patron M, Checchetto V, Raffaello A, Teardo E, Vecellio Reane D, Mantoan M, Granatiero V, Szabò I, De Stefani D, Rizzuto R. MICU1 and MICU2 finely tune the mitochondrial Ca2+ uniporter by exerting opposite effects on MCU activity. Mol Cell. 2014 Mar 6;53(5):726-37. doi: 10.1016/j.molcel.2014.01.013. Epub 2014 Feb 20. PubMed PMID: 24560927; PubMed Central PMCID: PMC3988891.
• Raffaello A, De Stefani D, Sabbadin D, Teardo E, Merli G, Picard A, Checchetto V, Moro S, Szabò I, Rizzuto R. The mitochondrial calcium uniporter is a multimer that can include a dominant-negative pore-forming subunit. EMBO J. 2013 Aug 28;32(17):2362-76. doi: 10.1038/emboj.2013.157. Epub 2013 Jul 30. PubMed PMID: 23900286; PubMed Central PMCID: PMC3771344.
• De Stefani D, Raffaello A, Teardo E, Szabò I, Rizzuto R. A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature. 2011 Jun 19;476(7360):336-40. doi: 10.1038/nature10230. PubMed PMID: 21685888; PubMed Central PMCID: PMC4141877.