From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways

Wang, Yaqiu; Kanneganti, Thirumala‐Devi

doi:10.1016/j.csbj.2021.07.038

Cited by 281 publications

(199 citation statements)

References 261 publications

(301 reference statements)

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“…The major types of PCD are pyroptosis, necroptosis, ferroptosis, and apoptosis ( Green, 2019 ; Bedoui et al, 2020 ); the first three types are considered lytic cell death, and apoptosis is considered non-lytic. These different forms of PCD can be distinguished by different initiators, effectors, and executioners ( Wang and Kanneganti, 2021 ).…”

Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

“…Notably, necroptosis is considered independent of capsases ( Conrad et al, 2016 ). Instead, upon initiation by receptors, necroptosis is mediated by RIPK1 or RIPK3-induced MLKL phosphorylation, followed by the formation of MLKL pores ( Wang and Kanneganti, 2021 ). Interestingly, necroptosis usually occurs when the extrinsic pathway of apoptosis is non-functional ( Frank and Vince, 2019 ).…”

Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

“…It is important to note that pyroptosis, necroptosis, ferroptosis, and apoptosis have different initiators, effectors, and executioners ( Wang and Kanneganti, 2021 ), and this is associated with differences in their histological and biochemical features ( Belavgeni et al, 2020 ; Li et al, 2020c ). All types of PCD except apoptosis are passive processes ( Norbury and Hickson, 2001 ).…”

Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

“…PCD is therefore an important component of homeostasis and also provides host defense against pathogens, cancer, and other pathologies ( Bedoui et al, 2020 ). The major types of PCD are pyroptosis, apoptosis, and necroptosis ( Wang and Kanneganti, 2021 ). Disturbances of extracellular or intracellular homeostasis that destroy innate immunity can lead to pyroptosis, also referred to as gasdermin (GSDM)-dependent programmed necrosis, the most recently defined type of PCD ( Jorgensen and Miao, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Sun

Zhou

et al. 2021

Front. Pharmacol.

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Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people’s attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.

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Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

Section: Comparison Of Pyroptosis Necroptosis Ferroptosis and Apoptosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Sun

Zhou

et al. 2021

Front. Pharmacol.

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“…6A). PANoptosis is a newly described type of cell death in which apoptosis, pyroptosis, and necroptosis pathways are all engaged in parallel following complex inflammasome triggers like HSV or Francisella novicida infection [109][110][111] . PANoptosis is driven by formation of the PANoptosome, a complex that coordinates the efforts of AIM2, ZBP1, and pyrin to promote caspase-1-, caspase-3,7,8-and MLKL-dependent inflammatory cell death 109 .…”

Section: Mito-damp Release Drives Necroptosis In Lrrk2 G2019s Macrophagesmentioning

confidence: 99%

Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection

Weindel

Zhao

Martinez

et al. 2021

Preprint

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SUMMARYHuman mutations in mitochondrial-associated genes are associated with inflammatory diseases and susceptibility to infection. However, their mechanistic contributions to immune outcomes remain ill-defined. We discovered that the disease-associated gain-of-function allele Lrrk2G2019S (leucine-rich repeat kinase 2) promotes mitochondrial hyper-fission, depolarization, and oxidative stress in macrophages. In the presence of Lrrk2G2019S-dependent mitochondrial perturbations, AIM2 inflammasome activation promotes more cell death but not more pyroptotic IL-1b release. Instead, inflammasome activation in Lrrk2G2019S macrophages triggers gasdermin D (GSDMD)-mediated mitochondrial pores, driving up ROS-mediated RIPK1/RIPK3/MLKL dependent necroptosis. Consequently, infection of Lrrk2G2019S mice with Mycobacterium tuberculosis elicits hyperinflammation and immunopathology via enhanced neutrophil infiltration. By uncovering that GSDMD promotes non-pyroptotic cell death in Lrrk2G2019S macrophages, our findings demonstrate that altered mitochondrial function can reprogram cell death modalities to elicit distinct immune outcomes. This provides mechanistic insights into why mutations in LRRK2 are associated with susceptibility to chronic inflammatory and infectious diseases.HIGHLIGHTSAltered mitochondrial homeostasis reprograms cell death modalitiesGSDMD associates with and depolarizes mitochondrial membranes following AIM2 activationGSDMD initiates a shift from pyroptotic to necroptotic cell death in Lrrk2G2019S macrophagesLrrk2G2019S elicits hyperinflammation and susceptibility to infection in flies and mice

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Ultrasmall Enzyodynamic PANoptosis Nano‐Inducers for Ultrasound‐Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition

Wei,

Wang,

Ren

et al. 2024

Advanced Materials

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Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi2Sn2O7 nanozyme with ultrasound‐magnified multienzyme‐mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N‐GSDMD, cleaved Caspase 1, p‐MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi2Sn2O7‐mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi2Sn2O7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma.

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From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways

Abstract: Graphical abstract

Cited by 281 publications

References 261 publications

Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Mini-Review: GSDME-Mediated Pyroptosis in Diabetic Nephropathy

Mitochondrial dysfunction promotes alternative gasdermin D-mediated inflammatory cell death and susceptibility to infection

Ultrasmall Enzyodynamic PANoptosis Nano‐Inducers for Ultrasound‐Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition

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