Mauro Piacentini
University of Rome Tor Vergata
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Publication
Featured researches published by Mauro Piacentini.
Cell Death & Differentiation | 2005
Guido Kroemer; Wafik S. El-Deiry; Pierre Golstein; Marcus E. Peter; David L. Vaux; Peter Vandenabeele; Boris Zhivotovsky; Mikhail V. Blagosklonny; Walter Malorni; Richard A. Knight; Mauro Piacentini; Shigekazu Nagata; Gerry Melino
Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like ‘percentage apoptosis’ and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that ‘autophagic cell death’ is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including ‘entosis’, ‘mitotic catastrophe’, ‘necrosis’, ‘necroptosis’ and ‘pyroptosis’.
Cell Death & Differentiation | 2012
Lorenzo Galluzzi; Ilio Vitale; John M. Abrams; Emad S. Alnemri; Eric H. Baehrecke; Mikhail V. Blagosklonny; Ted M. Dawson; Valina L. Dawson; Wafik S. El-Deiry; Simone Fulda; Eyal Gottlieb; Douglas R. Green; Michael O. Hengartner; Oliver Kepp; Richard A. Knight; Sharad Kumar; Stuart A. Lipton; Xin Lu; Frank Madeo; Walter Malorni; Patrick Mehlen; Gabriel Núñez; Marcus E. Peter; Mauro Piacentini; David C. Rubinsztein; Yufang Shi; Hans-Uwe Simon; Peter Vandenabeele; Eileen White; Junying Yuan
In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including ‘apoptosis’, ‘necrosis’ and ‘mitotic catastrophe’. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
Nature Medicine | 2007
Michel Obeid; Antoine Tesniere; François Ghiringhelli; Gian Maria Fimia; Lionel Apetoh; Jean Luc Perfettini; Maria Castedo; Grégoire Mignot; Theoharis Panaretakis; Noelia Casares; Didier Métivier; Nathanael Larochette; Peter van Endert; Fabiola Ciccosanti; Mauro Piacentini; Laurence Zitvogel; Guido Kroemer
Anthracyclin-treated tumor cells are particularly effective in eliciting an anticancer immune response, whereas other DNA-damaging agents such as etoposide and mitomycin C do not induce immunogenic cell death. Here we show that anthracyclins induce the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knockdown of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase 1/GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase 1/GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anticancer immune responses and delineate a possible strategy for immunogenic chemotherapy.
Nature | 2007
Gian Maria Fimia; Anastassia Stoykova; Alessandra Romagnoli; Luigi Giunta; Sabrina Di Bartolomeo; Roberta Nardacci; Marco Corazzari; Claudia Fuoco; Ahmet Ucar; Peter Schwartz; Peter Gruss; Mauro Piacentini; Kamal Chowdhury; Francesco Cecconi
Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals.
The EMBO Journal | 2004
Nicola Vahsen; Céline Candé; Jean Jacques Brière; Paule Bénit; Nicholas Joza; Nathanael Larochette; Pier G. Mastroberardino; Marie O. Pequignot; Noelia Casares; Vladimir Lazar; Olivier Feraud; Najet Debili; Silke Wissing; Silvia Engelhardt; Frank Madeo; Mauro Piacentini; Josef M. Penninger; Hermann Schägger; Pierre Rustin; Guido Kroemer
Apoptosis‐inducing factor (AIF) is a mitochondrial flavoprotein that, after apoptosis induction, translocates to the nucleus where it participates in apoptotic chromatinolysis. Here, we show that human or mouse cells lacking AIF as a result of homologous recombination or small interfering RNA exhibit high lactate production and enhanced dependency on glycolytic ATP generation, due to severe reduction of respiratory chain complex I activity. Although AIF itself is not a part of complex I, AIF‐deficient cells exhibit a reduced content of complex I and of its components, pointing to a role of AIF in the biogenesis and/or maintenance of this polyprotein complex. Harlequin mice with reduced AIF expression due to a retroviral insertion into the AIF gene also manifest a reduced oxidative phosphorylation (OXPHOS) in the retina and in the brain, correlating with reduced expression of complex I subunits, retinal degeneration, and neuronal defects. Altogether, these data point to a role of AIF in OXPHOS and emphasize the dual role of AIF in life and death.
Trends in Biochemical Sciences | 2002
László Fésüs; Mauro Piacentini
Transglutaminase 2 (TG2) is an inducible transamidating acyltransferase that catalyzes Ca(2+)-dependent protein modifications. It acts as a G protein in transmembrane signalling and as a cell surface adhesion mediator, this distinguishes it from other members of the transglutaminase family. The sequence motifs and domains revealed in the recent TG2 structure, can each be assigned distinct cellular functions, including the regulation of cytoskeleton, cell adhesion and cell death. Ablation of TG2 in mice results in impaired wound healing, autoimmunity and diabetes, reflecting the number and variety of TG2 functions. An important role for the enzyme in the pathogenesis of coeliac disease, fibrosis and neurodegenerative disorders has also been demonstrated, making TG2 an important therapeutic target.
Cell Death & Differentiation | 2009
Lorenzo Galluzzi; Stuart A. Aaronson; John M. Abrams; Emad S. Alnemri; David W. Andrews; Eric H. Baehrecke; Nicolas G. Bazan; Mikhail V. Blagosklonny; Klas Blomgren; Christoph Borner; Dale E. Bredesen; Catherine Brenner; Maria Castedo; John A. Cidlowski; Aaron Ciechanover; Gerald M. Cohen; V De Laurenzi; R De Maria; Mohanish Deshmukh; Brian David Dynlacht; Wafik S. El-Deiry; Richard A. Flavell; Simone Fulda; Carmen Garrido; Pierre Golstein; Marie Lise Gougeon; Douglas R. Green; Hinrich Gronemeyer; György Hajnóczky; J. M. Hardwick
Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
Journal of Clinical Investigation | 2009
María Salazar; Arkaitz Carracedo; Íñigo J. Salanueva; Sonia Hernández-Tiedra; Mar Lorente; Ainara Egia; Patricia Vázquez; Cristina Blázquez; Sofia Torres; Stéphane Garcia; Jonathan Nowak; Gian Maria Fimia; Mauro Piacentini; Francesco Cecconi; Pier Paolo Pandolfi; Luis González-Feria; Juan L. Iovanna; Manuel Guzmán; Patricia Boya; Guillermo Velasco
Autophagy can promote cell survival or cell death, but the molecular basis underlying its dual role in cancer remains obscure. Here we demonstrate that delta(9)-tetrahydrocannabinol (THC), the main active component of marijuana, induces human glioma cell death through stimulation of autophagy. Our data indicate that THC induced ceramide accumulation and eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation and thereby activated an ER stress response that promoted autophagy via tribbles homolog 3-dependent (TRB3-dependent) inhibition of the Akt/mammalian target of rapamycin complex 1 (mTORC1) axis. We also showed that autophagy is upstream of apoptosis in cannabinoid-induced human and mouse cancer cell death and that activation of this pathway was necessary for the antitumor action of cannabinoids in vivo. These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.
The EMBO Journal | 2015
Lorenzo Galluzzi; Federico Pietrocola; José Manuel Bravo-San Pedro; Ravi K. Amaravadi; Eric H. Baehrecke; Francesco Cecconi; Patrice Codogno; Jayanta Debnath; David A. Gewirtz; Vassiliki Karantza; Alec C. Kimmelman; Sharad Kumar; Beth Levine; Maria Chiara Maiuri; Seamus J. Martin; Josef M. Penninger; Mauro Piacentini; David C. Rubinsztein; Hans-Uwe Simon; Anne Simonsen; Andrew Thorburn; Guillermo Velasco; Kevin M. Ryan; Guido Kroemer
Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.
Journal of Cell Biology | 2010
Sabrina Di Bartolomeo; Marco Corazzari; Francesca Nazio; Serafina Oliverio; Gaia Lisi; Manuela Antonioli; Vittoria Pagliarini; Silvia Matteoni; Claudia Fuoco; Luigi Giunta; Marcello D'Amelio; Roberta Nardacci; Alessandra Romagnoli; Mauro Piacentini; Francesco Cecconi; Gian Maria Fimia
When autophagy is induced, ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from the cytoskeleton and allowing its relocalization to the ER membrane to nucleate autophagosome formation.