Research Interests
Contacts between organelles create microdomains that regulate key intracellular activities, signaling pathways, metabolic programs, and systemic homeostasis. Therefore, the study of inter-organelle contacts in biology bridges the gap between cell biology, cell physiology, and metabolism, enhancing our understanding of the evolution and organization of eukaryotic and metazoan complexity. In the Pellegrini Lab, our research focuses on investigating the function, structure, and dynamics of novel inter-organelle contacts.
One of our major discoveries was the identification and characterization of the contact between rough endoplasmic reticulum (ER) and mitochondria. In particular, we have recently reported the existence of a unique type of rough ER in liver cells that forms a wrapping structure around mitochondria and peroxisomes. We have named this ER "WrappER" to signify its role in enveloping other cellular organelles, namely mitochondria and peroxisomes. Through our studies, we have demonstrated that the WrappER plays a critical role in regulating the transport and metabolism of dietary lipids (fatty acids and cholesterol) within liver cell.
Currently, our research is focused on understanding the involvement of WrappER-mitochondria and WrappER-peroxisome contacts in liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma. We aim to unravel the mechanisms by which these inter-organelle contacts contribute to the development and progression of these liver diseases.
By investigating inter-organelle contacts, we strive to advance our knowledge of cellular processes and their implications in disease pathogenesis. Our findings may provide valuable insights into potential therapeutic targets for liver diseases and contribute to the broader understanding of inter-organelle communication and its impact on cellular function.
At the Pellegrini Lab, our focus extends beyond conducting world-class breakthrough research using cutting-edge technologies. We are also committed to training talented MSc and PhD students, providing them with the skills and knowledge necessary to identify, solve, and present complex problems using the scientific method. We believe in nurturing the next generation of Talents and equipping them with the tools to excel not only in their scientific pursuits but also in any other professional endeavor they choose to pursue. By building upon the research conducted in the Pellegrini Lab, our students develop critical thinking abilities, effective communication skills, and a strong work ethic that will serve them well in their future careers. Whether they continue in academia, enter industry, join the government or pursue other professional paths, our students leave the Pellegrini Lab equipped with the tools and mindset for success.
Publications
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Jeyaraju DV, Xu L, Letellier MC, Bandaru S, Zunino R, Berg EA, McBride HM, Pellegrini L. Phosphorylation and cleavage of presenilin-associated rhomboid-like protein (PARL) promotes changes in mitochondrial morphology. PNAS (2006) PMID: 17116872
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Cipolat S, Rudka T, Hartmann D, Costa V, Serneels L, Craessaerts K, Metzger K, Frezza C, Annaert W, D'Adamio L, Derks C, Dejaegere T, Pellegrini L, D'Hooge R, Scorrano L, De Strooper B. Mitochondrial rhomboid PARL regulates cytochrome c release during apoptosis via OPA1-dependent cristae remodeling. Cell (2006) PMID: 16839884
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Jeyaraju DV, Cisbani G, De Brito OM, Koonin EV, Pellegrini L. Hax1 lacks BH modules and is peripherally associated to heavy membranes: implications for Omi/HtrA2 and PARL activity in the regulation of mitochondrial stress and apoptosis. Cell Death & Differentiation. 2009 PMID: 19680265
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Jeyaraju DV, McBride HM, Hill RB, Pellegrini L. Structural and mechanistic basis of Parl activity and regulation. Cell Death & Differentiation (2011) PMID: 21415861
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Lavoie N, Jeyaraju DV, Peralta MR 3rd, Seress L, Pellegrini L, Tóth K. Vesicular zinc regulates the Ca2+ sensitivity of a subpopulation of presynaptic vesicles at hippocampal mossy fiber terminals. J Neurosci. (2011) PMID: 22171030
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Sood A, Jeyaraju DV, Prudent J, Caron A, Lemieux P, McBride HM, Laplante M, Tóth K, Pellegrini L. A Mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver. PNAS (2014) PMID: 25352671
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Giacomello M, Pellegrini L. The coming of age of the mitochondria-ER contact: a matter of thickness. Cell Death & Differentiation (2016) PMID: 27341186
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Glytsou C, Calvo E, Cogliati S, Mehrotra A, Anastasia I, Rigoni G, Raimondi A, Shintani N, Loureiro M, Vazquez J, Pellegrini L, Enriquez JA, Scorrano L, Soriano ME. Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control. Cell Reports (2016) PMID: 27974214
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Scorrano L, De Matteis MA, Emr S, Giordano F, Hajnóczky G, Kornmann B, Lackner LL, Levine TP, Pellegrini L, Reinisch K, Rizzuto R, Simmen T, Stenmark H, Ungermann C, Schuldiner M. Coming together to define membrane contact sites. Nature Communications (2019) PMID: 30894536
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Anastasia I, Ilacqua N, Raimondi A, Lemieux P, Ghandehari-Alavijeh R, Faure G, Mekhedov SL, Williams KJ, Caicci F, Valle G, Giacomello M, Quiroga AD, Lehner R, Miksis MJ, Toth K, de Aguiar Vallim TQ, Koonin EV, Scorrano L, Pellegrini L. Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis. Cell Reports (2021) PMID: 33730569
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Ilacqua N, Anastasia I, Pellegrini L. Isolation and analysis of fractions enriched in WrappER-associated mitochondria from mouse liver. STAR Protocols (2021) PMID: 34458870
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Ilacqua N, Anastasia I, Aloshyn D, Ghandehari-Alavijeh R, Peluso EA, Brearley-Sholto MC, Pellegrini LV, Raimondi A, de Aguiar Vallim TQ, Pellegrini L. Expression of Synj2bp in mouse liver regulates the extent of wrappER-mitochondria contact to maintain hepatic lipid homeostasis. Biology Direct (2022) PMID: 36457006
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Ilacqua N, Anastasia I, Raimondi A, Lemieux P, de Aguiar Vallim TQ, Toth K, Koonin EV, Pellegrini L. A three-organelle complex made by wrappER contacts with peroxisomes and mitochondria responds to liver lipid flux changes. J Cell Sci. (2022) PMID: 34672330
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Ilacqua N, Raimondi A, Pellegrini L. Liver inter-organelle membrane contact sites revealed by serial section electron tomography. Methods Cell Biol.(2023) PMID: 37451764
For a complete list of publications