Fulvio Reggiori, Ph.D.
Assistant Professor of Cell Biology
Telephone: +31.88.755 7652
Fax: +31.30.254 1797
Janice Griffith, technician:(firstname.lastname@example.org)
Ester Rieter, Ph.D. student: (email@example.com)
Aniek van der Vaart, Ph.D. student: (firstname.lastname@example.org)
Mustafa Ulasli, Ph.D. student: (email@example.com)
Muriel Mari, post-doc: (M.Mari@umcutrecht.nl)
Eduardo Cebollero, post-doc: (firstname.lastname@example.org)
Marinke van Oorschot, student: (email@example.com)
Remko Goossens, student (firstname.lastname@example.org)
Ana Maria Guzman Prieto, student (email@example.com) Molecular mechanism of autophagosome formation in the yeast Saccharomyces cerevisiae.
(with Janice Griffith, in collaboration with Hans Geuze)
Autophagy is a degradative process conserved among all eukaryotic cells and is required for the rapid degradation of large portions of the cytoplasm and unnecessary or damaged organelles in the lysosome lumen. It has long been known that this catabolic pathway is essential to generate an internal pool of nutrients that permit cells to survive during prolonged periods of starvation. Recent studies however, have revealed that autophagy actively participates in other cellular processes such as development, cellular differentiation and rearrangement, aging, elimination of aberrant structures and type II programmed cell death, as well as contributing to the cell’s defense against pathogens (both viruses and bacteria) and tumors. Consequently, defects in this protective barrier correlate with a growing list of diseases, including cancer, neurodegenerative disorders such as Huntington’s, Parkinson’s and Alzheimer’s diseases, and cardiomyopathies.
The main morphological feature of autophagy is the sequestration of the cargo targeted for destruction by a large cytosolic double-membrane vesicle called autophagosome that delivers it into the lysosome/vacuole interior for destruction. Despite the identification of many specific components, the molecular mechanism that directs formation of the sequestering vesicles remains largely unknown. Conceptual model of autophagy.The cargo destined for destruction is enwrapped by a membrane, leading to the formation of a double-membrane vesicle called an autophagosome. Once the sequestration process is completed, the autophagosome fuses with the lysosome/vacuole. During the fusion event, the external lipid bilayer of the autophagosome becomes part of the lysosome/vacuole surface, whereas the internal vesicle—now termed an autophagic body—is liberated into the interior of this organelle where, together with the cargo, it is degraded by resident hydrolases. [Reggiori F. and Klionsky D.J. (2005), Curr.Opin.Cell.Biol., 17, 415-422]
The model organism used in our studies is the yeast Saccharomyces cerevisiae, a unicellular eukaryote very suitable for either genetic or biochemical experimental approaches, which we combined with microscopy techniques (both fluorescence and electron microscopy) to try to unveil the mechanism of membrane assembly and sealing during autophagosome formation. Yeast autophagosomes. Autophagosomes are transient structures and in order stabilized it, we take advantage of a strain expressing a conditional allele of VAM3, a gene coding for a tSNARE required for the fusion of autophagosomes with the vacuole. The strain was nitrogen starved for 3 h at restrictive temperature before being prepared for electron microscopy. Examples of autophagosomes are indicated with an arrow. [Reggiori et al. (2001). J.Biol.Chem., 278, 5009-5020]
Reggiori F, Tooze S (2009), The emERgence of autophagosomes, Dev Cell, 17, 747-748.
Markgraf DF, Ahnert F, Henning A, Mari M, Epp N, Peplowska K Griffith J, Reggiori F*, Ungermann C (2009), The CORVET subunit Vps8 cooperates with the Rab5 homolog Vps21 to induce clustering of late endosomal compartments, Mol Biol Cell, 20, 5276-5289. *co-corresponding author
Cebollero E, Reggiori F (2009), Regulation of autophagy in yeast, Biochim Biophys Acta, 1793, 1413-1421.
Monastyrska I, Rieter E, Klionsky DJ, Reggiori F (2009), The role of cytoskeleton in autophagy, Biol Reviews, 84, 431-448.
Griffith J, Reggiori F (2009), Ultrastructural analysis of Nanogold-labelled endocytic compartments of yeast Saccharomyces cerevisiae using a cryo-sectioning procedure, J Histochem Cytochem, 57, 801-9.
Griffith J, Mari M, De Mazière A, Reggiori F (2008), A cryosectioning procedure for the ultrastructural analysis and the immunogold labelling of yeast S. cerevisiae, Traffic, 9, 1060-1072.
de Haan CAM, Reggiori F (2008), Are nidoviruses hijacking the autophagy machinery? Autophagy, 4, 276-279.
van der Vaart A, Mari M,Reggiori F (2008), A picky eater: Exploring the molecular mechanism of autophagy in human pathologies, Traffic, 3, 281–289.
Mari M, Reggiori F (2007), Shaping membranes into autophagosomes, Nat Cell Biol, 9, 1125-1127.
Reggiori F, Klionsky DJ (2006), Atg9 sorting from mitochondria is impaired in early secretion and VFT complex mutants in Saccharomyces cerevisiae, J Cell Sci, 119, 2903-2911.
Reggiori F (2006), Membrane origin for autophagy, Curr Top Dev Biol, 74, 1-30.
Reggiori F, Monastryrska I, Shintani T, Klionsky DJ (2005), The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae, Mol Biol Cell, 16, 5843-5856.
Reggiori F, Klionsky DJ (2005), Autophagosomes: Biogenesis from scratch?, Curr Opin Cell Biol, 17, 415-422.
Reggiori F, Shintani T, Nair U, Klionsky DJ (2005), Atg9 cycles between mitochondria and the pre-autophagosomal structure in yeasts, Autophagy, 1, 101-109.
Reggiori F, Wang CW, Nair U, Shintani T, Abeliovich H, Klionsky DJ (2004), Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae, Mol Biol Cell, 15, 189-204.
Reggiori F, Tucker KA, Stromhaug PE, Klionsky DJ (2004), The Apg1-Apg13 complex regulates Apg9 and Cvt23 retrieval transport from the pre-autophagosomal structure, Dev Cell, 6, 79-90.
Reggiori F, Klionsky DJ (2002), Autophagy in the eukaryotic cell, Eukaryot Cell, 1, 11-21.
Reggiori F, Pelham HRB (2002), A transmembrane ubiquitin ligase required to sort membrane proteins into multivesicular bodies, Nat Cell Biol, 4, 117-123.
Reggiori F, Pelham HRB (2001), Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting, EMBO J, 20, 5176-5186.
Reggiori F, Canivenc-Gansel E, Conzelmann A (1997), Lipid remodeling leads to the introduction and exchange of defined ceramides on GPI proteins in the ER and Golgi of Saccharomyces cerevisiae, EMBO J, 16, 3506-3518. Professional Career1994 - 1997
PhD study at the Department of Biochemistry, University of Fribourg, Switzerland (Supervisor: Prof. A. Conzelmann). 1997 - 1998
Postdoctoral fellow at the Department of Biochemistry with Prof. Andreas Conzelmann, University of Fribourg, Switzerland. 1998 - 2001
Postdoctoral fellow in the Laboratory of Cell Biology with Dr. Hugh R.B. Pelham at MRC Laboratory of Molecular Biology, Cambridge, United Kingdom. 2001 - 2005
Postdoctoral fellow at the Life Sciences Institute and the Department of Molecular, Cellular, and Developmental Biology with Prof. Daniel Klionsky, University of Michigan, Ann Arbor, United States. 2005 - current
Tenure-track Assistant Professor at the Department of Cell Biology, UMC Utrecht, The Netherlands.Awards, Honors
CIBA-GEIGY prize for the best 1993/1994 graduation curriculum in chemistry and biochemistry at the University of Fribourg.
Swiss National Science Foundation fellowship (1998-1999).
EMBO long-term fellowship (1999-2001)
EMBO long-term fellowship (2001-2002)
Swiss National Science Foundation fellowship for advanced researchers (2002-2004) Research Interests
Coronaviruses Financial support
2006: Utrecht University High Potential grant
2006: ZonMW VIDI grant
2007: ZonMW Medium Investment grant
2007: ALW Open Program grant