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

In the Brassicaceae, the dry stigma is an initial barrier to pollen acceptance as the stigmatic papillae lack surface secretions, and consequently rapid cellular responses are required to accept compatible pollen. Regulated secretion with secretory vesicles or multivesicular bodies is initiated in the stigmatic papillae towards the compatible pollen grain. In self-incompatible species, this basal compatible pollen response is superseded by the self-incompatibility signaling pathway where the secretory organelles are found in autophagosomes and vacuole for destruction. In this chapter, we describe a detailed protocol using the Transmission Electron Microscope to document the rapid cellular changes that occur in the stigmatic papillae in response to compatible versus self-incompatible pollen, at the pollen-stigma interface.

Following the Time-Course of Post-pollination Events by Transmission Electron Microscopy (TEM): Buildup of Exosome-Like Structures with Compatible Pollinations.

This invention relates to cells of a self-compatible hybrid plant, the parents of which are a homozygous self-incompatible female parent, and a homozygous male parent, and the nuclear genome of which contains a vector comprising a DNA sequence which, when expressed in a plant cell, imparts self-incompatibility to the plant, and a promoter capable of directing the expression of the DNA sequence in the cell. The invention includes the vector, a plant comprising the cells, a plant transformed with the vector, the seed of such plants, and a method for conferring the self-compatible phenotype on progeny of the self-incompatible female parent and self-compatible male parent. The invention comprises an improved self-pollination control system for hybrid seed production or breeding which, by using a knockout transgene to eliminate the self-incompatibility phenotype in hybrids, can result in increased yields.

Production of self-compatible brassica hybrids using a self-incompatible pollination control system

Receptor-Like Kinases (RLKs) have been discovered to regulate several signaling events during pollen–pistil interactions, with functions uncovered in both the pollen tube and the pistil. The earliest role is for S Receptor Kinase (SRK) in the rapid activation of the Brassicaceae self-incompatible response in the stigma following the perception of self-pollen. The next role is in the communication of a growing pollen tube with the transmitting tract of the Solanum lycopersicum pistils through the Pollen Receptor Kinases (LePRKs). Once the pollen tube has reached the ovule, it is fundamentally important for the pollen tube to have the correct timing to cease growth and release the sperm cells for the successful double fertilization of the egg cell and central cell. In Arabidopsis thaliana, this event is mediated by RLKs on both the female (FERONIA/SIRENE) and male (ANXUR1 and ANXUR2) side. Thus, RLKs play several fundamental roles in the successful creation of the next generation. This chapter will review the functions of these receptor kinases as well as other players that work alongside with these RLKs in regulating these precise steps during pollen–pistil interactions.

The Regulation of Pollen–Pistil Interactions by Receptor-Like Kinases

In plants, macroautophagy/autophagy is an essential mechanism responsible for a large variety of processes throughout the plant’s lifecycle, including nutrient processing, immunity, stress responses and senescence. Previous studies had observed the presence of autophagosomes in an Arabidopsis sexual reproduction system that prevents self-fertilization (self-incompatibility), but their requirement in this pathway was unclear. Using autophagy-deficient mutants, we have recently found that autophagy is a key contributor in the Arabidopsis self-incompatibility response to reject self-pollen. 

The role of autophagy in the Arabidopsis self-incompatible pollen rejection response

Successful reproduction in the Brassicaceae is mediated by a complex series of interactions between the pollen and the pistil, and some species have an additional layer of regulation with the self-incompatibility trait. While the initial activation of the self-incompatibility pathway by the pollen S-locus protein11/S-locus cysteine-rich peptide and the stigma S Receptor Kinase is well characterized, the downstream mechanisms causing self-pollen rejection are still not fully understood. In previous studies, we had detected the presence of autophagic bodies with self-incompatible pollinations in Arabidopsis lyrata and transgenic A. thaliana lines, but it was not known if autophagy was essential for self-pollen rejection. Here, we investigated the requirement of autophagy in this response by crossing mutations in the essential AUTOPHAGY7 (ATG7) or AUTOPHAGY5 (ATG5) genes into two different transgenic self-incompatible A. thaliana lines in the Col-0 and C24 accessions. By using these previously characterized transgenic lines that express A. lyrata and A. halleri self-incompatibility genes, we demonstrated that disrupting autophagy can weaken their self-incompatible responses in the stigma. When the atg7 or atg5 mutations were present, an increased number of self-incompatible pollen were found to hydrate and form pollen tubes that successfully fertilized the self-incompatible pistils. Additionally, we confirmed the presence of GFP-ATG8a labelled autophagosomes in the stigmatic papillae following self-incompatible pollinations. Together, these findings support the requirement of autophagy in the self-incompatibility response and add to the growing understanding of the cellular events that take place in the stigma to reject self-pollen.

/pdf/autophagy-is-required-for-the-rejection-of-self-incompatible-2u7j1n9y9o.pdf

Daphne R. Goring

Papers

Following the Time-Course of Post-pollination Events by Transmission Electron Microscopy (TEM): Buildup of Exosome-Like Structures with Compatible Pollinations.

Production of self-compatible brassica hybrids using a self-incompatible pollination control system

The Regulation of Pollen–Pistil Interactions by Receptor-Like Kinases

The role of autophagy in the Arabidopsis self-incompatible pollen rejection response

Autophagy is required for the rejection of self-incompatible pollen in two accessions of transgenic Arabidopsis thaliana