Mechanistic cell biology Working Group
The Mitochondrial dynamics during cell division Working Group, led by Dr. Valentina Piano, investigates the molecular signalling pathways that control mitochondrial fission and redistribution in mitosis, and how defects in these mechanisms can cause chromosome instability and aneuploidy.
Mitochondrial abnormalities are hallmarks of numerous disorders, including many of the pathologies studied in the Institute (e.g. Alzheimer disease, spinal muscular atrophies, skeletal disorders). Given the limited knowledge of the effects of impaired mitochondrial dynamics on cell cycle and chromosome segregation, the possible physiological outcomes are often neglected, although they may synergically contribute to the development of the pathological phenotypes.
We study these complex cellular processes through a bottom-up approach. We use in vitro reconstitution to identify key protein-protein interactions that can subsequently be perturbed in living human cells to elucidate the role of each specific protein in the mitotic regulation of mitochondrial fission. Our experimental approach constitutes a unique setup to investigate the unexplored effects of known pathological mutations and provide molecular explanations for complex cellular phenotypes associated to rare genetic disorders and degenerative diseases.
Piano V, Alex A, Stege P, Maffini S, Stoppiello GA, Huis In 't Veld PJ, Vetter IR, Musacchio A. CDC20 assists its catalytic incorporation in the mitotic checkpoint complex.
Science. 2021 Jan 1;371(6524):67-71.
PubMed PMID: 33384373
Alex A, Piano V, Polley S, Stuiver M, Voss S, Ciossani G, Overlack K, Voss B, Wohlgemuth S, Petrovic A, Wu Y, Selenko P, Musacchio A, Maffini S.
Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology.
Elife. 2019 Jul 16;8:e48287
PubMed PMID: 31310234
Piano V, Benjamin DI, Valente S, Nenci S, Marrocco B, Mai A, Aliverti A, Nomura DK, Mattevi A. Discovery of Inhibitors for the Ether Lipid-Generating Enzyme AGPS as Anti-Cancer Agents.
ACS Chem Biol. 2015 Nov 20;10(11):2589-97
PubMed PMID: 26322624
Nenci S, Piano V, Rosati S, Aliverti A, Pandini V, Fraaije MW, Heck AJ, Edmondson DE, Mattevi A. Precursor of ether phospholipids is synthesized by a flavoenzyme through covalent catalysis.
Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18791-6.
PubMed PMID: 23112191
