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.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

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

Microbe-associated molecular patterns (MAMPs) are molecular signatures typical of whole classes of microbes, and their recognition plays a key role in innate immunity. Endogenous elicitors are similarly recognized as damage-associated molecular patterns (DAMPs). This review focuses on the diversity of MAMPs/DAMPs and on progress to identify the corresponding pattern recognition receptors (PRRs) in plants. The two best-characterized MAMP/PRR pairs, flagellin/FLS2 and EF-Tu/EFR, are discussed in detail and put into a phylogenetic perspective. Both FLS2 and EFR are leucine-rich repeat receptor kinases (LRR-RKs). Upon treatment with flagellin, FLS2 forms a heteromeric complex with BAK1, an LRR-RK that also acts as coreceptor for the brassinolide receptor BRI1. The importance of MAMP/PRR signaling for plant immunity is highlighted by the finding that plant pathogens use effectors to inhibit PRR complexes or downstream signaling events. Current evidence indicates that MAMPs, DAMPs, and effectors are all perceived as danger signals and induce a stereotypic defense response.

A Renaissance of Elicitors: Perception of Microbe-Associated Molecular Patterns and Danger Signals by Pattern-Recognition Receptors

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.

/pdf/molecular-definitions-of-cell-death-subroutines-q5g428rlyi.pdf

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Autophagy is a mechanism by which cellular material is delivered to lysosomes for degradation, leading to the basal turnover of cell components and providing energy and macromolecular precursors. Autophagy has opposing, context-dependent roles in cancer, and interventions to both stimulate and inhibit autophagy have been proposed as cancer therapies. This has led to the therapeutic targeting of autophagy in cancer to be sometimes viewed as controversial. In this Review, we suggest a way forwards for the effective targeting of autophagy by understanding the context-dependent roles of autophagy and by capitalizing on modern approaches to clinical trial design.

/pdf/targeting-autophagy-in-cancer-2pjcn0h04a.pdf

Targeting autophagy in cancer

Much of plant physiology, growth, and development is controlled by the selective removal of short-lived regulatory proteins. One important proteolytic pathway involves the small protein ubiquitin (Ub) and the 26S proteasome, a 2-MDa protease complex. In this pathway, Ub is attached to proteins destined for degradation; the resulting Ub-protein conjugates are then recognized and catabolized by the 26S proteasome. This review describes our current understanding of the pathway in plants at the biochemical, genomic, and genetic levels, using Arabidopsis thaliana as the model. Collectively, these analyses show that the Ub/26S proteasome pathway is one of the most elaborate regulatory mechanisms in plants. The genome of Arabidopsis encodes more than 1400 (or >5% of the proteome) pathway components that can be connected to almost all aspects of its biology. Most pathway components participate in the Ub-ligation reactions that choose with exquisite specificity which proteins should be ubiquitinated. What remains to be determined is the identity of the targets, which may number in the thousands in plants.

/pdf/the-ubiquitin-26s-proteasome-proteolytic-pathway-3szv2gdxjk.pdf

The ubiquitin 26S proteasome proteolytic pathway

The sporophytic self-incompatibility (SI) system, which operates in the Brassicaceae is primarily controlled by two multi-allelic loci, encoding the SP11/SCR pollen ligand, and the stigma-specific S Receptor Kinase (SRK). Haplotypespecific recognition of SP11/SCR by SRK triggers the activation of SRK's intracellular kinase domain. This is predicted to cause the phosphorylation-mediated recruitment of the ARC1 E3 ubiquitin ligase. ARC1 is predicted to inhibit its substrate by ubiquitination, and recentwork suggests that Exo70A1 is a target of ARC1. Exo70A1 is predicted to regulate targeted secretion and is required in the stigma to promote compatible pollen hydration, germination and pollen tube growth. SRK is also known to interact with a number of other proteins, including the M locus protein kinase (MLPK), which may function with SRK to co-regulate ARC1. Here we review our present knowledge of the various cellular components that act in concert during the SI response.We also discuss the cellular mechanisms of how SI can cause pollen rejection through the inhibition of stigmatic factors that promote compatible pollen acceptance.

‘Self’ Pollen Rejection Through the Intersection of Two Cellular Pathways in the Brassicaceae: Self-Incompatibility and the Compatible Pollen Response

Phosphoinositides are important lipids involved in membrane identity, vesicle trafficking, and intracellular signaling. In recent years, phosphoinositides have been shown to play a critical role in polarized secretion in plants, as perturbations of phosphoinositide metabolism, through loss of function mutants, result in defects in root hair elongation and pollen tube growth, where polarized secretion occurs rapidly. In the Brassicaceae, responses of stigmatic papillae to compatible pollen are also thought to involve highly regulated secretory events to facilitate pollen hydration and penetration of the pollen tube through the stigmatic surface. We therefore sought to analyze the female sporophyte fertility of the root hair defective4-1 mutant and the PI 4-kinase β1/β2 double mutant, which differentially affect phosphatidylinositol-4-phosphate (PI4P) levels. Stigmas from both mutants supported slower rates of pollen grain hydration, and the fecundity of these mutants was also diminished as a result of failed pollination events. This study therefore concludes that PI4P is integral to appropriate pistil responses to compatible pollen.

Misregulation of phosphoinositides in Arabidopsis thaliana decreases pollen hydration and maternal fertility

Cell-cell signaling during the Brassicaceae self-incompatibility response.

Here we describe protein-protein interactions between signaling components in the conserved self-incompatibility pathway from Brassica spp. and Arabidopsis lyrata. Previously, we had demonstrated that ARC1 is necessary in A. lyrata for the rejection of self-pollen by the self-incompatibility pathway. The results described here demonstrate that A. lyrata ARC1 interacts with A. lyrata S Receptor Kinase (SRK1) in the yeast 2-hybrid system. A. lyrata ARC1 also interacted with B. napus SRK910 illustrating that interactions in this pathway are conserved across species. Finally, we discuss how the more widely occurring interactions between SRK and ARC1-related family members may be modulated in vivo by expression and subcellular localization patterns resulting in a particular response.

https://www.tandfonline.com/doi/pdf/10.1080/15592324.2016.1188233

Daphne R. Goring

Papers

‘Self’ Pollen Rejection Through the Intersection of Two Cellular Pathways in the Brassicaceae: Self-Incompatibility and the Compatible Pollen Response

Misregulation of phosphoinositides in Arabidopsis thaliana decreases pollen hydration and maternal fertility

Cell-cell signaling during the Brassicaceae self-incompatibility response.

Yeast two-hybrid interactions between Arabidopsis lyrata S Receptor Kinase and the ARC1 E3 ligase

The Search for Components of the Self-incompatibility Signalling Pathway(s) in Brassica napus