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

Id1 Overexpression Induces Tetraploidization and Multiple Abnormal Mitotic Phenotypes by Modulating Aurora A

The basic helix-loop-helix transcription factor, Id1, was shown to induce tetraploidy in telomerase-immortalized nasopharyngeal epithelial cells in this study. Using both transient and stable Id1-expressing cell models, multiple mitotic aberrations were detected, including centrosome amplification, binucleation, spindle defects, and microtubule perturbation. Many of these abnormal phenotypes have previously been reported in cells overexpressing Aurora A. Further experiments showed that Id1 could stabilize Aurora A, whereas knocking down Aurora A expression in Id1-expressing cells could rescue some of the mitotic defects. The mechanisms by which Aurora A could be modulated by Id1 were explored. DNA amplification of the Aurora A locus was not involved. Id1 could only weakly activate the transcriptional activity of the Aurora A promoter. We found that Id1 overexpression could affect Aurora A degradation, leading to its stabilization. Aurora A is normally degraded from mitosis exit by the APC/CCdh1-mediated proteasomal proteolysis pathway. Our results revealed that Id1 and Cdh1 are binding partners. The association of Id1 and Cdh1 was found to be dependent on the canonical destruction box motif of Id1, the increased binding of which may compete with the interaction between Cdh1 and Aurora A, leading to stabilization of Aurora A in Id1-overexpressing cells

Emerging roles of the unfolded protein response (UPR) in the nervous system: A link with adaptive behavior to environmental stress?

Stressors elicit a neuroendocrine response leading to increased levels of glucocorticoids, allowing the organism to adapt to environmental changes and maintain homeostasis. Glucocorticoids have a broad effect in the body, modifying the activity of the immune system, metabolism, and behavior through the activation of receptors in the limbic system. Chronic exposition to stressors operates as a risk factor for psychiatric diseases such as depression and posttraumatic stress disorder. Among the cellular alterations observed as a consequence of environmental stress, alterations to organelle function at the level of mitochondria and endoplasmic reticulum (ER) are emerging as possible factors contributing to neuronal dysfunction. ER proteostasis alterations elicit the unfolded protein response (UPR), a conserved signaling network that re-establish protein homeostasis. In addition, in the context of brain function, the UPR has been associated to neurodevelopment, synaptic plasticity and neuronal connectivity. Recent studies suggest a role of the UPR in the adaptive behavior to stress, suggesting a mechanistic link between environmental and cellular stress. Here, we revise recent evidence supporting an evolutionary connection between the neuroendocrine system and the UPR to modulate behavioral adaptive responses.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 3190596 1180186 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDAP 15150012 ECOS CONICYT Cooperation grant Chile-France ECOS170032 Takeda Pharmaceutical Company Ltd P09-015-F European Commission RD MSCA-RISE 734749 Michael J Fox Foundation for Parkinson's Research-Target Validation grant 9277 FONDEF ID16I10223 D11E1007 United States Department of Defense Air Force Office of Scientific Research (AFOSR) FA9550-16-1-0384 ALSRP Therapeutic Idea Award AL150111 Muscular Dystrophy Association 382453 CONICYT-Brazil 441921/2016-