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Cell Jan 2024Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by... (Review)
Review
Cell death supports morphogenesis during development and homeostasis after birth by removing damaged or obsolete cells. It also curtails the spread of pathogens by eliminating infected cells. Cell death can be induced by the genetically programmed suicide mechanisms of apoptosis, necroptosis, and pyroptosis, or it can be a consequence of dysregulated metabolism, as in ferroptosis. Here, we review the signaling mechanisms underlying each cell-death pathway, discuss how impaired or excessive activation of the distinct cell-death processes can promote disease, and highlight existing and potential therapies for redressing imbalances in cell death in cancer and other diseases.
Topics: Humans; Apoptosis; Cell Death; Ferroptosis; Homeostasis; Pyroptosis; Signal Transduction
PubMed: 38242081
DOI: 10.1016/j.cell.2023.11.044 -
Cell Communication and Signaling : CCS Aug 2023Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is... (Review)
Review
Short-chain fatty acids (SCFAs) are the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract. The absorption of SCFAs is mediated by substrate transporters, such as monocarboxylate transporter 1 and sodium-coupled monocarboxylate transporter 1, which promote cellular metabolism. An increasing number of studies have implicated metabolites produced by microorganisms as crucial executors of diet-based microbial influence on the host. SCFAs are important fuels for intestinal epithelial cells (IECs) and represent a major carbon flux from the diet, that is decomposed by the gut microbiota. SCFAs play a vital role in multiple molecular biological processes, such as promoting the secretion of glucagon-like peptide-1 by IECs to inhibit the elevation of blood glucose, increasing the expression of G protein-coupled receptors such as GPR41 and GPR43, and inhibiting histone deacetylases, which participate in the regulation of the proliferation, differentiation, and function of IECs. SCFAs affect intestinal motility, barrier function, and host metabolism. Furthermore, SCFAs play important regulatory roles in local, intermediate, and peripheral metabolisms. Acetate, propionate, and butyrate are the major SCFAs, they are involved in the regulation of immunity, apoptosis, inflammation, and lipid metabolism. Herein, we review the diverse functional roles of this major class of bacterial metabolites and reflect on their ability to affect intestine, metabolic, and other diseases. Video Abstract.
Topics: Fatty Acids, Volatile; Butyrates; Propionates; Gastrointestinal Tract; Apoptosis
PubMed: 37596634
DOI: 10.1186/s12964-023-01219-9 -
Experimental & Molecular Medicine Aug 2023Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically,... (Review)
Review
Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse cell death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed cell death. Thus, dysfunctional cellular pathways eventually lead or contribute to various age-related diseases, such as neurodegenerative, cardiovascular and metabolic diseases. Thus, mitochondrion-associated programmed cell death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli and that maintain cellular homeostasis via mitohormesis, the mitochondrial unfolded protein response, and mitophagy. The review also presents details on various forms of mitochondria-associated programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and paraptosis, and highlights their involvement in age-related disease pathogenesis, collectively suggesting therapeutic directions for further research.
Topics: Apoptosis; Mitochondria; Cell Death; Pyroptosis
PubMed: 37612409
DOI: 10.1038/s12276-023-01046-5 -
Biomedicine & Pharmacotherapy =... Jul 2023Recently, cuproptosis has been demonstrated to be a new non-apototic cell death mode that is characterized by copper dependence and the regulation of mitochondrial... (Review)
Review
Recently, cuproptosis has been demonstrated to be a new non-apototic cell death mode that is characterized by copper dependence and the regulation of mitochondrial respiration. Cuproptosis is distinct from known cell death modes such as apoptosis, necrosis, pyroptosis, or ferroptosis. Excessive copper induces cuproptosis by promoting protein toxic stress reactions via copper-dependent anomalous oligomerization of lipoylation proteins in the tricarboxylic acid (TCA) cycle and reducing iron-sulfur cluster protein levels. Ferredoxin1 (FDX1) promotes dihydrolipoyl transacetylase (DLAT) lipoacylation and abates iron-sulfur cluster proteins by reducing Cu to Cu, inducing cell death. Copper homeostasis depends on the copper transporter, and disturbances to this homeostasis cause cuproptosis. Recent evidence has shown that cuproptosis plays a significant role in the occurrence and development of many cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R) injury, heart failure, atherosclerosis, and arrhythmias. Copper chelators, such as ammonium tetrathiomolybdate(VI) and DL-Penicillamine, may ease the above cardiovascular diseases by inhibiting the cuproptosis pathway. Oxidative phosphorylation inhibitors may inhibit cuproptosis by inhibiting protein stress response. In conclusion, cuproptosis plays an essential role in cardiovascular disease pathogenesis. Inhibition of cardiovascular cuproptosis is expected to become a potential treatment. Here, we will thoroughly review the molecular mechanisms involved in cuproptosis and its significance in cardiovascular disease.
Topics: Humans; Cardiovascular Diseases; Copper; Heart Failure; Apoptosis; Sulfur; Iron
PubMed: 37150036
DOI: 10.1016/j.biopha.2023.114830 -
Experimental & Molecular Medicine Aug 2023Death is the inevitable fate of all living organisms, whether at the individual or cellular level. For a long time, cell death was believed to be an undesirable but... (Review)
Review
Death is the inevitable fate of all living organisms, whether at the individual or cellular level. For a long time, cell death was believed to be an undesirable but unavoidable final outcome of nonfunctioning cells, as inflammation was inevitably triggered in response to damage. However, experimental evidence accumulated over the past few decades has revealed different types of cell death that are genetically programmed to eliminate unnecessary or severely damaged cells that may damage surrounding tissues. Several types of cell death, including apoptosis, necrosis, autophagic cell death, and lysosomal cell death, which are classified as programmed cell death, and pyroptosis, necroptosis, and NETosis, which are classified as inflammatory cell death, have been described over the years. Recently, several novel forms of cell death, namely, mitoptosis, paraptosis, immunogenic cell death, entosis, methuosis, parthanatos, ferroptosis, autosis, alkaliptosis, oxeiptosis, cuproptosis, and erebosis, have been discovered and advanced our understanding of cell death and its complexity. In this review, we provide a historical overview of the discovery and characterization of different forms of cell death and highlight their diversity and complexity. We also briefly discuss the regulatory mechanisms underlying each type of cell death and the implications of cell death in various physiological and pathological contexts. This review provides a comprehensive understanding of different mechanisms of cell death that can be leveraged to develop novel therapeutic strategies for various diseases.
Topics: Humans; Cell Death; Apoptosis; Necrosis; Pyroptosis; Inflammation
PubMed: 37612413
DOI: 10.1038/s12276-023-01078-x -
International Journal of Molecular... Oct 2023PANoptosis is a newly defined programmed cell death (PCD) triggered by a series of stimuli, and it engages three well-learned PCD forms (pyroptosis, apoptosis,... (Review)
Review
PANoptosis is a newly defined programmed cell death (PCD) triggered by a series of stimuli, and it engages three well-learned PCD forms (pyroptosis, apoptosis, necroptosis) concomitantly. Normally, cell death is recognized as a strategy to eliminate unnecessary cells, inhibit the proliferation of invaded pathogens and maintain homeostasis; however, vigorous cell death can cause excessive inflammation and tissue damage. Acute lung injury (ALI) and chronic obstructive pulmonary syndrome (COPD) exacerbation is related to several pathogens (e.g., influenza A virus, SARS-CoV-2) known to cause PANoptosis. An understanding of the mechanism and specific regulators may help to address the pathological systems of these diseases. This review presents our understanding of the potential mechanism of PANoptosis and the role of PANoptosis in different pulmonary diseases.
Topics: Humans; Apoptosis; Cell Death; Acute Lung Injury; Homeostasis; Inflammation; Pyroptosis
PubMed: 37895022
DOI: 10.3390/ijms242015343 -
Trends in Molecular Medicine Jan 2024The innate immune system initiates cell death pathways in response to pathogens and cellular stress. Cell death can be either non-lytic (apoptosis) or lytic (PANoptosis,... (Review)
Review
The innate immune system initiates cell death pathways in response to pathogens and cellular stress. Cell death can be either non-lytic (apoptosis) or lytic (PANoptosis, pyroptosis, and necroptosis). PANoptosis has been identified as an inflammatory, lytic cell death pathway driven by caspases and RIPKs that is regulated by PANoptosome complexes, making it distinct from other cell death pathways. Several PANoptosome complexes (including ZBP1-, AIM2-, RIPK1-, and NLRP12-PANoptosomes) have been characterized to date. Furthermore, PANoptosis is implicated in infectious and inflammatory diseases, cancers, and homeostatic perturbations. Therefore, targeting its molecular components offers significant potential for therapeutic development. This review covers PANoptosomes and their assembly, PANoptosome-mediated cell death mechanisms, and ongoing progress in developing therapeutics that target PANoptosis.
Topics: Humans; Inflammasomes; Cell Death; Apoptosis; Caspases; Homeostasis
PubMed: 37977994
DOI: 10.1016/j.molmed.2023.10.001 -
Signal Transduction and Targeted Therapy Jan 2024Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the... (Review)
Review
Ischemia-reperfusion (I/R) injury paradoxically occurs during reperfusion following ischemia, exacerbating the initial tissue damage. The limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic interventions. The Wnt signaling pathway exhibits extensive crosstalk with various other pathways, forming a network system of signaling pathways involved in I/R injury. This review article elucidates the underlying mechanisms involved in Wnt signaling, as well as the complex interplay between Wnt and other pathways, including Notch, phosphatidylinositol 3-kinase/protein kinase B, transforming growth factor-β, nuclear factor kappa, bone morphogenetic protein, N-methyl-D-aspartic acid receptor-Ca-Activin A, Hippo-Yes-associated protein, toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β, and hepatocyte growth factor/mesenchymal-epithelial transition factor. In particular, we delve into their respective contributions to key pathological processes, including apoptosis, the inflammatory response, oxidative stress, extracellular matrix remodeling, angiogenesis, cell hypertrophy, fibrosis, ferroptosis, neurogenesis, and blood-brain barrier damage during I/R injury. Our comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery, while activation of the non-canonical Wnt pathways exacerbates injury. Moreover, we explore novel therapeutic approaches based on these mechanistic findings, incorporating evidence from animal experiments, current standards, and clinical trials. The objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction, to facilitate the development of innovative therapeutic agents for I/R injury.
Topics: Animals; Reperfusion Injury; Reperfusion; Wnt Signaling Pathway; Apoptosis; Ischemia
PubMed: 38185705
DOI: 10.1038/s41392-023-01688-x -
Seminars in Immunology Nov 2023Neutrophils are among the most abundant immune cells, representing about 50%- 70% of all circulating leukocytes in humans. Neutrophils rapidly infiltrate inflamed... (Review)
Review
Neutrophils are among the most abundant immune cells, representing about 50%- 70% of all circulating leukocytes in humans. Neutrophils rapidly infiltrate inflamed tissues and play an essential role in host defense against infections. They exert microbicidal activity through a variety of specialized effector mechanisms, including phagocytosis, production of reactive oxygen species, degranulation and release of secretory vesicles containing broad-spectrum antimicrobial factors. In addition to their homeostatic turnover by apoptosis, recent studies have revealed the mechanisms by which neutrophils undergo various forms of regulated cell death. In this review, we will discuss the different modes of regulated cell death that have been described in neutrophils, with a particular emphasis on the current understanding of neutrophil pyroptosis and its role in infections and autoinflammation.
Topics: Humans; Neutrophils; Pyroptosis; Phagocytosis; Apoptosis
PubMed: 37939552
DOI: 10.1016/j.smim.2023.101849 -
Biomedicine & Pharmacotherapy =... Dec 2023Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose... (Review)
Review
Diabetes mellitus is a metabolic disease caused by disorders of insulin secretion and utilization. Long-term hyperglycemia, insulin resistance, and disorders of glucose and lipid metabolism cause vascular endothelial cell damage. Endothelial dysfunction is a key feature of diabetic vascular complications such as diabetic nephropathy, retinopathy, neuropathy, and atherosclerosis. Importantly, cell death is thought to be a key factor contributing to vascular endothelial injury. Morphologically, cell death can be divided into three forms: type I apoptosis, type II autophagy, and type III necrosis. According to the difference in function, cell death can be divided into accidental cell death (ACD) and regulated cell death (RCD). RCD is a controlled process involving numerous proteins and precise signaling cascades. Multiple subroutines covered by RCD may be involved in diabetic endothelial dysfunction, including apoptosis, autophagy, necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, cuproptosis, and PANoptosis. This article briefly reviews the mechanism and significance of cell death associated with diabetic endothelial dysfunction, which will help deepen the understanding of diabetic endothelial cell death and provide new therapeutic ideas.
Topics: Humans; Cell Death; Diabetes Mellitus; Apoptosis; Necrosis; Regulated Cell Death
PubMed: 37918258
DOI: 10.1016/j.biopha.2023.115802