Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes
Lorenzo Galluzzi,Lorenzo Galluzzi,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,Klas Blomgren,Christoph Borner,Dale E. Bredesen,Dale E. Bredesen,Catherine Brenner,Maria Castedo,Maria Castedo,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,Richard A. Flavell,Simone Fulda,Carmen Garrido,Carmen Garrido,Pierre Golstein,Pierre Golstein,Pierre Golstein,Marie-Lise Gougeon,Douglas R. Green,Hinrich Gronemeyer,Hinrich Gronemeyer,Hinrich Gronemeyer,György Hajnóczky,J. M. Hardwick,Michael O. Hengartner,Hidenori Ichijo,Marja Jäättelä,Oliver Kepp,Oliver Kepp,Oliver Kepp,Adi Kimchi,Daniel J. Klionsky,Richard A. Knight,Sally Kornbluth,Sharad Kumar,Beth Levine,Beth Levine,Stuart A. Lipton,Enrico Lugli,Frank Madeo,Walter Malorni,Jean-Christophe Marine,Seamus J. Martin,Jan Paul Medema,Patrick Mehlen,Patrick Mehlen,Gerry Melino,Gerry Melino,Ute M. Moll,Ute M. Moll,Eugenia Morselli,Eugenia Morselli,Eugenia Morselli,Shigekazu Nagata,Donald W. Nicholson,Pierluigi Nicotera,Gabriel Núñez,Moshe Oren,Josef M. Penninger,Shazib Pervaiz,Marcus E. Peter,Mauro Piacentini,Jochen H. M. Prehn,Hamsa Puthalakath,Gabriel A. Rabinovich,Rosario Rizzuto,Cecília M. P. Rodrigues,David C. Rubinsztein,Thomas Rudel,Luca Scorrano,Hans-Uwe Simon,Hermann Steller,Hermann Steller,J. Tschopp,Yoshihide Tsujimoto,Peter Vandenabeele,Ilio Vitale,Ilio Vitale,Ilio Vitale,Karen H. Vousden,Richard J. Youle,Junying Yuan,Boris Zhivotovsky,Guido Kroemer,Guido Kroemer,Guido Kroemer +103 more
Reads0
Chats0
TLDR
A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.Abstract:
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 cellsread more
Citations
More filters
Journal ArticleDOI
The many substrates and functions of NEDD4-1
Xi Huang,Jing Chen,Wen Cao,Li Yang,Qingxiao Chen,Jingsong He,Qing Yi,He Huang,Enfan Zhang,Zhen Cai +9 more
TL;DR: NEDD4-1 likely acts as a novel drug target or diagnostic marker in the battle against cancer and is introduced to the latest potential therapeutic strategies that inhibit or activate NEDD 4-1 activity using small molecules.
Journal ArticleDOI
Lyapunov exponents and phase diagrams reveal multi‐factorial control over TRAIL‐induced apoptosis
Bree B. Aldridge,Bree B. Aldridge,Suzanne Gaudet,Douglas A. Lauffenburger,Peter K. Sorger,Peter K. Sorger +5 more
TL;DR: Factors controlling type I versus II phenotypes are investigated by performing Lyapunov exponent analysis of an ODE‐based model of cell death, predicting that the ratio of XIAP to pro‐caspase‐3 concentrations plays a key regulatory role and extending phase space analysis to mutations affecting the rate of caspasing ubiquitylation, predicting and showing that such mutations abolish all‐or‐none control over activation of effector caspases.
Journal ArticleDOI
The ULK1-FBXW5-SEC23B nexus controls autophagy
Yeon-Tae Jeong,Daniele Simoneschi,Sarah Keegan,David B. Melville,Natalia S. Adler,Anita Saraf,Laurence Florens,Michael P. Washburn,Michael P. Washburn,Claudio N. Cavasotto,Claudio N. Cavasotto,David Fenyö,Ana Maria Cuervo,Mario Rossi,Michele Pagano +14 more
TL;DR: It is proposed that, in the presence of nutrients, FBXW5 limits COPII-mediated autophagosome biogenesis, and inhibition of this event by ULK1 ensures efficient execution of the autophagic cascade in response to nutrient starvation.
Journal ArticleDOI
Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinase.
Hui Ding,Hui Ding,Guohua Zhang,Ka Wai Thomas Sin,Zhelong Liu,Zhelong Liu,Ren Kuo Lin,Min Li,Yi-Ping Li +8 more
TL;DR: Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation, but the intracellular signalling mechanism that mediates ActR IIB‐activated muscle catabolism is poorly defined.
Journal ArticleDOI
Therapeutic targeting of autophagy in cancer. Part I: Molecular pathways controlling autophagy
TL;DR: This review provides an overview of the signalling pathways that influence autophagy, particularly in cancer cells and illustrates that interference with multiple of these signalling pathways can have significant effects on cancer cell survival.
References
More filters
Journal ArticleDOI
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
TL;DR: The extent of tissue-PCD revealed by this method is considerably greater than apoptosis detected by nuclear morphology, and thus opens the way for a variety of studies.
Journal ArticleDOI
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
TL;DR: In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process.
Journal ArticleDOI
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
TL;DR: It is shown here that this morphological change is closely associated with excision of nucleosome chains from nuclear chromatin, apparently through activation of an intracellular, but non-lysosomal, endonuclease.
Journal ArticleDOI
Molecular characterization of mitochondrial apoptosis-inducing factor
Santos A. Susin,Hans K. Lorenzo,Naoufal Zamzami,Isabel Marzo,Bryan E. Snow,Joan Mangion,Etienne Jacotot,Paola Costantini,Markus Loeffler,Nathanael Larochette,David R. Goodlett,Ruedi Aebersold,David P. Siderovski,Josef M. Penninger,Guido Kroemer +14 more
TL;DR: The identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei is reported, indicating that AIF is a mitochondrial effector of apoptotic cell death.
Journal ArticleDOI
Mitochondrial Membrane Permeabilization in Cell Death
TL;DR: Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria, meaning that mitochondria coordinate the late stage of cellular demise.
Related Papers (5)
Classification of cell death: recommendations of the Nomenclature Committee on Cell Death
Guido Kroemer,Guido Kroemer,Guido Kroemer,Lorenzo Galluzzi,Lorenzo Galluzzi,Lorenzo Galluzzi,Peter Vandenabeele,John M. Abrams,Emad S. Alnemri,Eric H. Baehrecke,Mikhail V. Blagosklonny,Wafik S. El-Deiry,Pierre Golstein,Pierre Golstein,Douglas R. Green,Michael O. Hengartner,Richard A. Knight,Sharad Kumar,Stuart A. Lipton,Stuart A. Lipton,Stuart A. Lipton,Walter Malorni,Gabriel Núñez,Marcus E. Peter,Juerg Tschopp,Junying Yuan,Mauro Piacentini,Boris Zhivotovsky,Gerry Melino,Gerry Melino +29 more