DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells

Tarayrah-Ibraheim, Lama; Maurice, Elital Chass; Hadary, Guy; Ben-Hur, Sharon; Kolpakova, Alina; Braun, Tslil; Peleg, Yoav; Yacobi-Sharon, Keren; Arama, Eli

doi:10.1038/s41467-021-22622-1

Cited by 12 publications

(10 citation statements)

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“…the proper assembly of the mitochondrial respiratory complex I [52]. Interestingly, AIF seems a node in the p53-mediated RCD network, as apoptosis, parthanatos, and programmed necrosis could be connected with one another through this mitochondrial protein [53,54] (Fig. 1).…”

Section: P53 Might Increase Sensitization To Cuproptosis By Inhibitin...mentioning

confidence: 98%

“…p53 promotes LMP to facilitate nuclear translocation of DNase II with the help of AIF. DNase II then cleaves the DNA to activate the PARP1-AIF axis [ 54 ]. Also, p53, together with SIRT6, can directly activate PARP1 to induce parthanatos [ 89 ].…”

Section: Perspective On Mechanisms Underlying P53 Regulation Of Cupro...mentioning

confidence: 99%

“…Another p53-target gene, AIF , which encodes a mitochondrial membrane protein, is required for efficient oxidative phosphorylation as it is involved in the proper assembly of the mitochondrial respiratory complex I [ 52 ]. Interestingly, AIF seems a key node in the p53-mediated RCD network, as apoptosis, parthanatos, and programmed necrosis could be connected with one another through this mitochondrial protein [ 53 , 54 ] (Fig. 1 ).…”

Section: Perspective On Mechanisms Underlying P53 Regulation Of Cupro...mentioning

confidence: 99%

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Cuproptosis: p53-regulated metabolic cell death?

Chen

Hao

et al. 2023

Cell Death Differ

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Cuproptosis is a novel type of copper-induced cell death that primarily occurs in cells that utilize oxidative phosphorylation as the main metabolic pathway to produce energy. Copper directly associates with the lipoylated proteins of the tricarboxylic acid cycle, leading to the disulfide-bond-dependent aggregation of these lipoylated proteins, destabilization of the iron-sulfur cluster proteins, and consequent proteotoxic stress. Cancer cells prefer glycolysis (Warburg effect) to oxidative phosphorylation for producing intermediate metabolites and energy, thereby achieving resistance to cuproptosis. Interestingly, the tumor suppressor p53 is a crucial metabolic regulator that inhibits glycolysis and drives a metabolic switch towards oxidative phosphorylation in cancer cells. Additionally, p53 regulates the biogenesis of iron-sulfur clusters and the copper chelator glutathione, which are two critical components of the cuproptotic pathway, suggesting that this tumor suppressor might play a role in cuproptosis. Furthermore, the possible roles of mutant p53 in regulating cuproptosis are discussed. In this essay, we review the recent progress in the understanding of the mechanism underlying cuproptosis, revisit the roles of p53 in metabolic regulation and iron-sulfur cluster and glutathione biosynthesis, and propose several potential mechanisms for wild-type and mutant p53-mediated cuproptosis regulation.

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Section: P53 Might Increase Sensitization To Cuproptosis By Inhibitin...mentioning

confidence: 98%

Section: Perspective On Mechanisms Underlying P53 Regulation Of Cupro...mentioning

confidence: 99%

Section: Perspective On Mechanisms Underlying P53 Regulation Of Cupro...mentioning

confidence: 99%

See 1 more Smart Citation

Cuproptosis: p53-regulated metabolic cell death?

Chen

Hao

et al. 2023

Cell Death Differ

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“…This expansive advancement in the understanding of the gasdermin family and its activating protease enzymes, such as inflammatory caspase 4/5/11 [ 112 , 221 ], non-inflammatory caspase 3/7/8 [ 222 , 223 ], Cathepsin G [ 224 ] and neutrophil elastase [ 225 ], as well as inflammasome activation [ 226 , 227 ], has further broadened the concept of cell death as critical therapeutic targets [ 228 , 229 ] in host immunity [ 230 , 231 ], microbial-induced hyperinflammation [ 140 , 232 ], cytokine storm syndrome [ 228 ] and autoimmune diseases [ 209 , 233 ], as well as in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 228 , 234 ]. Today, program cell deaths (PCD), particularly pyroptosis along with others, such as Necroptosis [ 235 ], Ferroptosis [ 236 ], NETosis [ 104 , 237 ], Parthanatos [ 238 ] and PANoptosis [ 133 , 135 ], have received a lot of attention from all facets of research disciplines. Fortunately, in spite of scrupulous attention to unravel the underlying molecular mechanism, the phenomenon of immunological cell death is still progressively complicated [ 239 ].…”

Section: Nod-like Receptors In the Regulation Of Pyroptosis Cell Deathmentioning

confidence: 99%

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

Babamale

Chen

2021

IJMS

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Cell death is an essential immunological apparatus of host defense, but dysregulation of mutually inclusive cell deaths poses severe threats during microbial and parasitic infections leading to deleterious consequences in the pathological progression of infectious diseases. Nucleotide-binding oligomerization domain (NOD)-Leucine-rich repeats (LRR)-containing receptors (NLRs), also called nucleotide-binding oligomerization (NOD)-like receptors (NLRs), are major cytosolic pattern recognition receptors (PRRs), their involvement in the orchestration of innate immunity and host defense against bacteria, viruses, fungi and parasites, often results in the cleavage of gasdermin and the release of IL-1β and IL-18, should be tightly regulated. NLRs are functionally diverse and tissue-specific PRRs expressed by both immune and non-immune cells. Beyond the inflammasome activation, NLRs are also involved in NF-κB and MAPK activation signaling, the regulation of type I IFN (IFN-I) production and the inflammatory cell death during microbial infections. Recent advancements of NLRs biology revealed its possible interplay with pyroptotic cell death and inflammatory mediators, such as caspase 1, caspase 11, IFN-I and GSDMD. This review provides the most updated information that caspase 8 skews the NLRP3 inflammasome activation in PANoptosis during pathogen infection. We also update multidimensional roles of NLRP12 in regulating innate immunity in a content-dependent manner: novel interference of NLRP12 on TLRs and NOD derived-signaling cascade, and the recently unveiled regulatory property of NLRP12 in production of type I IFN. Future prospects of exploring NLRs in controlling cell death during parasitic and microbial infection were highlighted.

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“…Previous studies have suggested that monocrotaline and Sugen/hypoxia (SuHx) induce PH in rats by increasing the apoptosis of the right ventricular myocardium via numerous pathways (Neto-Neves et al, 2017). The main mechanisms of parthanatos are overactivation of PARP-1/PAR in the nucleus and transfer to the mitochondria, as well as mitochondrial AIF nuclear translocation and the transfer of macrophage MIF by AIF to the nucleus, resulting in DNA cleavage thereby creating large fragments (Tarayrah-Ibraheim et al, 2021;Wang et al, 2011Wang et al, , 2016Zhou et al, 2021). PARP-1, PAR, AIF, and MIF are therefore key factors in parthanatos.…”

Section: Introductionmentioning

confidence: 99%

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

Wang

et al. 2021

Am J Mens Health

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There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan–Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all p < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all p < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all p < .005). Patients with PARP-1 levels <11.24 ng/mL or AIF levels <1.459 pg/mL had significantly better survival than those with higher PARP-1 or AIF levels ( p < .0001). Circulating levels of PARP-1 and AIF were independent predictors for PH onset and mortality, which indicated that parthanatos might be associated with the pathogenesis of PH.

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DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells

Cited by 12 publications

References 101 publications

Cuproptosis: p53-regulated metabolic cell death?

Cuproptosis: p53-regulated metabolic cell death?

Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections

Impact of Parthanatos on the Increased Risk of Onset and Mortality in Male Patients With Pulmonary Hypertension

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