Copper homeostasis and cuproptosis in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 23, 2022

As an essential micronutrient, copper is required for a wide range of physiological processes in virtually all cell types. Because the accumulation intracellular can induce oxidative stress and perturbing cellular function, homeostasis tightly regulated. Recent studies identified novel copper-dependent form death called cuproptosis, which distinct from other known pathways underlying death. Cuproptosis occurs via binding to lipoylated enzymes tricarboxylic acid (TCA) cycle, leads subsequent protein aggregation, proteotoxic stress, ultimately Here, we summarize our current knowledge regarding metabolism, copper-related disease, characteristics mechanisms that regulate cuproptosis. In addition, discuss implications cuproptosis pathogenesis various disease conditions, including Wilson's neurodegenerative diseases, cancer, therapeutic potential targeting

Language: Английский

---

Cuproptosis: a copper-triggered modality of mitochondrial cell death

Cell Research, Journal Year: 2022, Volume and Issue: 32(5), P. 417 - 418

Published: March 30, 2022

Language: Английский

---

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

---

Cuproptosis: mechanisms and links with cancers

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: March 7, 2023

Abstract Cuproptosis was a copper-dependent and unique kind of cell death that separate from existing other forms death. The last decade has witnessed considerable increase in investigations programmed death, whether copper induced an independent form long been argued until mechanism cuproptosis revealed. After that, increasing number researchers attempted to identify the relationship between process cancer. Thus, this review, we systematically detailed systemic cellular metabolic processes copper-related tumor signaling pathways. Moreover, not only focus on discovery its mechanism, but also outline association cancers. Finally, further highlight possible therapeutic direction employing ion ionophores with cuproptosis-inducing functions combination small molecule drugs for targeted therapy treat specific

Language: Английский

---

Copper-induced cell death

Science, Journal Year: 2022, Volume and Issue: 375(6586), P. 1231 - 1232

Published: March 17, 2022

Excess copper causes mitochondrial protein aggregation and triggers a distinct form of cell death.

Language: Английский

---

Copper-dependent autophagic degradation of GPX4 drives ferroptosis

Autophagy, Journal Year: 2023, Volume and Issue: 19(7), P. 1982 - 1996

Published: Jan. 9, 2023

Ferroptosis is a type of iron-dependent regulated cell death characterized by unrestricted lipid peroxidation and membrane damage. Although GPX4 (glutathione peroxidase 4) plays master role in blocking ferroptosis eliminating phospholipid hydroperoxides, the regulation remains poorly understood. Here, we report an unexpected for copper promoting ferroptotic death, but not cuproptosis, inducing macroautophagic/autophagic degradation GPX4. Copper chelators reduce sensitivity do inhibit other types such as apoptosis, necroptosis, alkaliptosis. Conversely, exogenous increases ubiquitination formation aggregates directly binding to protein cysteines C107 C148. TAX1BP1 (Tax1 1) then acts autophagic receptor subsequent response stress. Consequently, enhances ferroptosis-mediated tumor suppression mouse model pancreatic cancer tumor, whereas attenuate experimental acute pancreatitis associated with ferroptosis. Taken together, these findings provide new insights into link between metal stress autophagy-dependent death.Abbreviations: CALCOCO2, calcium coiled-coil domain 2; GPX4, glutathione 4; MAP1LC3A/B, microtubule 1 light chain 3 alpha/beta; MPO, myeloperoxidase; NCOA4, nuclear coactivator OPTN, optineurin; PDAC, ductal adenocarcinoma; RIPK1, interacting serine/threonine kinase 1; ROS, reactive oxygen species; SLC40A1, solute carrier family 40 member SQSTM1, sequestosome TAX1BP1, Tax1 TEPA, tetraethylenepentamine; TM, tetrathiomolybdate.

Language: Английский

---

Copper metabolism in cell death and autophagy

Autophagy, Journal Year: 2023, Volume and Issue: 19(8), P. 2175 - 2195

Published: April 14, 2023

Copper is an essential trace element in biological systems, maintaining the activity of enzymes and function transcription factors. However, at high concentrations, copper ions show increased toxicity by inducing regulated cell death, such as apoptosis, paraptosis, pyroptosis, ferroptosis, cuproptosis. Furthermore, can trigger macroautophagy/autophagy, a lysosome-dependent degradation pathway that plays dual role regulating survival or death fate cells under various stress conditions. Pathologically, impaired metabolism due to environmental genetic causes implicated variety human diseases, rare Wilson disease common cancers. Therapeutically, copper-based compounds are potential chemotherapeutic agents be used alone combination with other drugs approaches treat cancer. Here, we review progress made understanding metabolic processes their impact on regulation autophagy. This knowledge may help design future clinical tools improve cancer diagnosis treatment.

Language: Английский

---

An Enzyme‐Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(43)

Published: Sept. 2, 2022

Abstract Cuproptosis, a newly identified form of regulated cell death that is copper‐dependent, offers great opportunities for exploring the use copper‐based nanomaterials inducing cuproptosis cancer treatment. Here, glucose oxidase (GOx)‐engineered nonporous copper(I) 1,2,4‐triazolate ([Cu(tz)]) coordination polymer (CP) nanoplatform, denoted as GOx@[Cu(tz)], starvation‐augmented and photodynamic synergistic therapy developed. Importantly, catalytic activity GOx shielded in scaffold but can be “turned on” efficient depletion only upon glutathione (GSH) stimulation cells, thereby proceeding starvation therapy. The GSH sensitizes cells to GOx@[Cu(tz)]‐mediated cuproptosis, producing aggregation lipoylated mitochondrial proteins, target copper‐induced toxicity. increased intracellular hydrogen peroxide (H 2 O ) levels, due oxidation glucose, activates type I (PDT) efficacy GOx@[Cu(tz)]. vivo experimental results indicate GOx@[Cu(tz)] produces negligible systemic toxicity inhibits tumor growth by 92.4% athymic mice bearing 5637 bladder tumors. This thought first report cupreous nanomaterial capable cuproptosis‐based cancer, which should invigorate studies pursuing rational design efficacious strategies based on cuproptosis.

Language: Английский

---

Cuproptosis: a new form of programmed cell death

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(8), P. 867 - 868

Published: April 22, 2022

Language: Английский

---

Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery

International Journal of Surgery, Journal Year: 2022, Volume and Issue: 107, P. 106936 - 106936

Published: Sept. 20, 2022

Postoperative progression and chemotherapy resistance is the major cause of treatment failure in patients with triple-negative breast cancer (TNBC). Currently, there a lack an ideal predictive model for drug sensitivity postoperative TNBC patients. Diverse programmed cell death (PCD) patterns play important role tumor progression, which has potential to be prognostic indicator after surgery.Twelve PCD (apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic death, netotic parthanatos, lysosome-dependent autophagy-dependent alkaliptosis, oxeiptosis) were analyzed construction. Bulk transcriptome, single-cell genomics, clinical information collected from TCGA-BRCA, METABRIC, GSE58812, GSE21653, GSE176078, GSE75688, KM-plotter cohorts validate model.The machine learning algorithm established index (CDI) 12-gene signature. Validated five independent datasets, high CDI had worse prognosis surgery. Two molecular subtypes distinct vital biological processes identified by unsupervised clustering model. A nomogram performance was constructed incorporating features. Furthermore, associated immune checkpoint genes key microenvironment components integrated analysis bulk transcriptome. are resistant standard adjuvant regimens (docetaxel, oxaliplatin, etc.); however, they might sensitive palbociclib (an FDA-approved luminal cancer).Generally, we novel comprehensively analyzing diverse patterns, can accurately predict user-friendly website created facilitate application this prediction (https://tnbc.shinyapps.io/CDI_Model/).

Language: Английский

---