Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.


Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.






Published Version (Please cite this version)


Publication Info

Galluzzi, Lorenzo, Ilio Vitale, Stuart A Aaronson, John M Abrams, Dieter Adam, Patrizia Agostinis, Emad S Alnemri, Lucia Altucci, et al. (2018). Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell death and differentiation, 25(3). pp. 486–541. 10.1038/s41418-017-0012-4 Retrieved from

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Francis Ka-Ming Chan

Adjunct Professor in the Department of Immunology

Our lab is interested in how cell death impacts innate inflammation and immune responses.  We have a long-standing interest in the biology and signaling mechanism of tumor necrosis factor (TNF), a key cytokine that regulates many inflammatory diseases (e.g. rheumatoid arthritis, inflammatory bowel diseases etc), pathogen infections, and cancer.  Several key discoveries made by the PI during his graduate school and postdoctoral training include identification of one of the first cell cycle inhibitors, INK4d-p19 (Mol Cell Biol. 1995, cited over 300 times), and the discovery of the "pre-ligand assembly domain (PLAD)" that mediates TNF receptors signal transduction (Science 2000, cited over 800 times).

In recent years, we have focused our effort on elucidating the signaling mechanism of a novel form of inflammatory cell death termed necroptosis.  In 2009, our group identified Receptor Interacting Protein kinase 3 (RIPK3) as a central mediator of necroptosis (Cell, 2009, cited over 1000 times).  Current projects include (1) deciphering the signaling mechanisms of necroptosis, (2) interrogation of the biology of RIPK3 and related necroptosis signaling molecules in intestinal wound healing and inflammation, (3) elucidation of the role of necroptosis in pathogen infections, and many others. 

We aim to take the knowledge we gain from basic pathway discovery to better understand the principles of immune regulation.  We believe our endeavor will pave the way for more efficacious therapeutic intervention in auto-inflammatory diseases, cancers and pathogen infections.

Current research projects in the lab include the following broad areas.  Interested students and postdoctoral candidates are encouraged to contact Dr. Chan for more information on rotation projects and research opportunities.

1. The role of necroptosis signal adaptors in inflammatory diseases
We are interested in how the kinases RIPK1 and RIPK3, both of which have critical functions in cell death, contribute to injury-induced inflammation and tissue repair.  Currently, we are using mouse models of intestinal injury and inflammation to study the function of these signal adaptors in intestinal homeostasis.

2. The role of cell death in anti-viral immune responses
We have discovered that necroptosis is an important innate immune defense mechanism against certain viruses.  We are interested in how host cell death during pathogen infections can alter the course of the host immune response.  On the other hand, we are also interested in exploring the mechanisms employed by different viral pathogens in combating the host cell death machinery.

3. Signaling mechanism of RIP kinases in cell death and inflammation
We found that the RIP kinases can promote inflammation through cell death-dependent and independent mechanisms.  What are the molecular events that regulate the diverse functions of the RIP kinases?  We are using biochemical, cell biological, and genetic tools to dissect the molecular regulation of these important immune signaling molecules.

Colin S Duckett

Professor of Pathology

Edward A. Miao

Chancellor's Distinguished Professor of Immunology

Programmed cell death directly counteracts intracellular infection by eliminating compromised host cells.


Pyroptotic cell death triggered by caspase-1/11 was described in 1992, but remained a possible cell culture artifact for many years. We were the first to use in vivo animal models to demonstrate that pyroptosis clears intracellular bacteria. Pyroptosis traps the bacteria within the cellular remains while simultaneously attracting neutrophils to kill them.


Intracellular bacteria use type III secretion (T3S) to inject virulence effectors that reprogram host cells. We discovered that the NLRC4 inflammasome activates caspase-1 in response to T3S activity. The subcellular location of the detection event is of critical importance. Whereas extracellular flagellin sensed by TLR5 leads to proinflammatory transcriptional responses, we discovered that T3S-injected cytosolic flagellin triggers caspase-1 activation and pyroptosis.


Bacterial lipopolysaccharide (LPS) is the most potent immune-stimulating microbial molecule. The discovery that TLR4 detects extracellular LPS reinvigorated innate immunity research. We discovered that caspase-11 detects LPS in the mammalian cytosol. Again, the responses to LPS are drastically different depending on where the detection occurs. Extracellular LPS sensed by TLR4 drives proinflammatory transcription. Cytosolic LPS activates caspase-11 causing pyroptosis, which eradicates cytosol-invasive bacteria. However, aberrant caspase-11 activation is an extremely dangerous driver of sepsis.


We found that bona fide pathogens evade these defenses. Therefore, to study basic components of innate immunity we pioneer the use of environmental bacteria with pathogenic potential that have not adapted to evade mammalian immunity. These “pathogens” are experimental tools that reveal previously under-appreciated aspects of innate immunity. We find that environmental pathogens are useful tools with which to study the innate immune system, for example, we study pathogens such as Chromobacterium violaceum that infects patients with chronic granulomatous disease (who carry defects in the NADPH oxidase and cannot generate reactive oxygen in the phagosome).

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.