Magalí F. Scocozza , Ulises A. Zitare , Pablo Cancian , María A. Castro , Lígia O. Martins , Daniel H. Murgida
{"title":"Molecular basis of H2O2/O2.−/.OH discrimination during electrochemical activation of DyP peroxidases: The critical role of the distal residues","authors":"Magalí F. Scocozza , Ulises A. Zitare , Pablo Cancian , María A. Castro , Lígia O. Martins , Daniel H. Murgida","doi":"10.1016/j.jinorgbio.2024.112816","DOIUrl":"10.1016/j.jinorgbio.2024.112816","url":null,"abstract":"<div><div>Here, we show that the replacement of the distal residues Asp and/or Arg of the DyP peroxidases from <em>Bacillus subtilis</em> and <em>Pseudomonas putida</em> results in functional enzymes, albeit with spectroscopically perturbed active sites. All the enzymes can be activated either by the addition of exogenous H<sub>2</sub>O<sub>2</sub> or by in situ electrochemical generation of the reactive oxygen species (ROS) <sup>•</sup>OH, O<sub>2</sub><sup>•-</sup> and H<sub>2</sub>O<sub>2</sub>. The latter method leads to broader and upshifted pH-activity profiles. Both WT enzymes exhibit a differential predominance of ROS involved in their electrochemical activation, which follows the order <sup>•</sup>OH > O<sub>2</sub><sup>•-</sup> > H<sub>2</sub>O<sub>2</sub> for BsDyP and O<sub>2</sub><sup>•-</sup> > H<sub>2</sub>O<sub>2</sub> > <sup>•</sup>OH for PpDyP. This ROS selectivity is preserved in mutants with unperturbed sites but is blurred out for distorted sites. The underlying molecular basis of the selectivity mechanisms is analysed through molecular dynamics simulations, which reveal distorted hydrogen bonding networks and higher throughput of the access tunnels in the variants exhibiting no selectivity. The electrochemical activation method provides superior performance for protein variants with a high prevalence of the alternative <sup>•</sup>OH and O<sub>2</sub><sup>•-</sup> species. These results constitute a promising advance towards engineering DyPs for electrocatalytic applications.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112816"},"PeriodicalIF":3.8,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Silva-Brea , J. Aduriz-Arrizabalaga , D. De Sancho , X. Lopez
{"title":"Designing mimosine-containing peptides as efficient metal chelators: Insights from molecular dynamics and quantum calculations","authors":"D. Silva-Brea , J. Aduriz-Arrizabalaga , D. De Sancho , X. Lopez","doi":"10.1016/j.jinorgbio.2024.112807","DOIUrl":"10.1016/j.jinorgbio.2024.112807","url":null,"abstract":"<div><div>Mimosine, a non-essential amino acid derived from plants, has a strong affinity for binding divalent and trivalent metal cations, including Zn<sup>2+</sup>, Ni<sup>2+</sup>, Fe<sup>2+/3+</sup>, and Al<sup>3+</sup>. This ability endows mimosine with significant antimicrobial and anti-cancer properties, making it a promising candidate for therapeutic applications. Previous research has demonstrated the effectiveness of mimosine-containing peptides as metal chelators, offering a safer alternative to conventional chelation agents. However, optimizing the design of these peptides necessitates a thorough understanding of their conformational ensembles in both free and metal-bound states. Here, we perform an in-depth analysis of mimosine-containing peptides using long-time MD simulations and quantum calculations to identify key factors critical for peptide design. Our results show that these peptides can achieve metal-binding affinities comparable to established aluminum chelators like deferiprone and citrate. Additionally, we underscore the crucial role of the peptide backbone in reducing the entropic penalty associated with metal binding. We propose strategies to modulate this entropic penalty—a challenging thermodynamic property to evaluate but essential in complexes between short peptides and metals—by incorporating proline residues and optimizing sequence length. These approaches offer promising pathways for developing efficient peptide chelators.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112807"},"PeriodicalIF":3.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Barry Arkles , David Segarnick , Leandro C. Clementino , Keith H. Pannell , Andrew P. Thomas
{"title":"Silacrown ethers as ion transport modifiers and preliminary observations of cardiovascular cell line response","authors":"Barry Arkles , David Segarnick , Leandro C. Clementino , Keith H. Pannell , Andrew P. Thomas","doi":"10.1016/j.jinorgbio.2024.112814","DOIUrl":"10.1016/j.jinorgbio.2024.112814","url":null,"abstract":"<div><div>Crown ethers have been shown to have physiological effects ascribed to their ionophoric properties. However, high levels of toxicity precluded interest in their evaluation as therapeutic agents. We prepared new silacrown analogs of crown ethers. These initial studies focused on examples of large ring silacrown ethers having at least fourteen ring atoms with at least one lipophilic or hydrophobic substituent on the ring and/or on the silicon atom. The synthesis of silacrown ethers, ionophoric behavior, toxicity studies, and preliminary pharmacodynamic studies in cardiac myocyte cell lines are presented and compared to their carbon analogs. We report the effects of these compounds in HL-1 cells, an atrial muscle cell line with plasma membrane and sarcoplasmic reticulum Ca<sup>2+</sup> channels that give rise to spontaneous Ca<sup>2+</sup> transients driven by action potentials. Dicyclohexano-18-crown-6 and the silacrown equivalent dimethylsila-17-cyclohexanocrown-6 were both found to rapidly inhibit the Ca<sup>2+</sup> transients after acute treatment, and these effects were reversed when extracellular KCl was increased to cause plasma membrane depolarization. The data suggest that the silacrowns can mimic the effects of crown ethers with similar ring sizes, and this appears to be due to their effects on membrane potential and suppression of action potential firing.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"265 ","pages":"Article 112814"},"PeriodicalIF":3.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Copper complexes induce haem oxygenase-1 (HMOX1) and cause apoptotic cell death in pancreatic cancer cells","authors":"Zakeeya Jhetam , Carla Martins-Furness , Cathy Slabber , Orde Q. Munro , Marietha Nel , Leonie Harmse","doi":"10.1016/j.jinorgbio.2024.112815","DOIUrl":"10.1016/j.jinorgbio.2024.112815","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic malignancy, has a dismal 5-year survival rate, making palliative chemotherapy the only treatment option. Targeted therapy has limited efficacy in PDAC, underscoring the need for novel therapeutic approaches. The inducible stress-response protein, haem oxygenase-1 (HMOX1), has been implicated in treatment failure in PDAC.</div><div>Copper coordination complexes have shown promise as anticancer agents against various cancers, and are associated with apoptotic cell death. The different ligands to which copper is complexed, determine the specificity and efficacy of each complex.</div><div>Three different classes of copper complexes were evaluated for anti-cancer activity against AsPC-1 and MIA PaCa-2 pancreatic cancer cell lines. A copper-phenanthroline-theophylline complex (CuPhTh<sub>2</sub>), a copper-8-aminoquinoline-naphthyl complex (Cu8AqN), and two copper-aromatic-isoindoline complexes (CuAIsI) were effective inhibitors of cell proliferation with clinically relevant IC<sub>50</sub> values below 5 μM. The copper complexes caused reactive oxygen species (ROS) formation, promoted annexin-V binding, disrupted the mitochondrial membrane potential (MMP) and activated caspase-9 and caspase-3/7, confirming apoptotic cell death.</div><div>Expression of nuclear HMOX1 was increased in both cell lines, with the CuPhTh<sub>2</sub> complex being the most active. Inhibition of HMOX1 activity significantly decreased the IC<sub>50</sub> values of these copper complexes suggesting that HMOX1 inhibition may alter treatment outcomes in PDAC.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112815"},"PeriodicalIF":3.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A critical analysis of the potential of iron heterobimetallic complexes in anticancer research","authors":"Boglárka Tűz , Isabel Correia , Paulo N. Martinho","doi":"10.1016/j.jinorgbio.2024.112813","DOIUrl":"10.1016/j.jinorgbio.2024.112813","url":null,"abstract":"<div><div>Due to their diverse chemical properties and high ability to interact with biological molecules and cellular processes, transition metal-based compounds have emerged as promising candidates for cancer therapy. Iron complexes are among them, however, there is a gap in the comprehensive analysis of heterometallic iron complexes in the anticancer field. This review aims to fill this gap by summarizing recent progress in the study of Fe(II) and Fe(III) heterobimetallic complexes for anticancer applications and to gather important insights and future perspectives, with special emphasis on their theranostic capabilities. Works published between 2014 and 2024 were considered in this critical survey, that covers a range of complex types, including ferrocene in bimetallic complexes with Pt, Pd, Au, Ag, Ru, Rh, Ir, Cu, Re, Sn and Co; organometallic Fe-complexes with Ru and Ag; photoactive metal complexes with Pt and Co; and magnetic resonance imaging contrast agents with Gd and Mn. Studies conducted to determine the modes of action are highlighted and suggest the involvement of the metal species in reactive oxygen species generation within cells, the impact on apoptosis and cell cycle arrest, and many others. By pursuing interdisciplinary research, innovative theranostic platforms with enhanced efficacy, specificity, and clinical relevance can be developed for cancer management.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112813"},"PeriodicalIF":3.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerda T. Gátszegi , Tatsiana V. Petrasheuskaya , Nóra V. May , Bálint Hajdu , Gabriella Spengler , Felix Bacher , Sergiu Shova , Vladimir B. Arion , Éva A. Enyedy
{"title":"Solution equilibrium and redox properties of metal complexes with 2-formylpyridine guanylhydrazone derivatives: Effect of morpholine and piperazine substitutions","authors":"Gerda T. Gátszegi , Tatsiana V. Petrasheuskaya , Nóra V. May , Bálint Hajdu , Gabriella Spengler , Felix Bacher , Sergiu Shova , Vladimir B. Arion , Éva A. Enyedy","doi":"10.1016/j.jinorgbio.2024.112812","DOIUrl":"10.1016/j.jinorgbio.2024.112812","url":null,"abstract":"<div><div>Schiff bases derived from aminoguanidine are extensively investigated for their structural versatility. The tridentate 2-formylpyridine guanylhydrazones act as analogues of 2-formyl or 2-acetylpyridine thiosemicarbazones, where the thioamide unit is replaced by the guanidyl group. Six derivatives of 2-formylpyridine guanylhydrazone were synthesized and their proton dissociation and complex formation processes with Cu(II), Fe(II) and Fe(III) ions were studied using pH-potentiometry, UV–visible, NMR and electron paramagnetic resonance spectroscopic methods. The ligands have substituents such as amine, morpholine, <em>N</em>-methyl-piperazine at different positions of the pyridine ring. The influence of the different structural elements on the solution chemical properties and cytotoxicity has been disclosed. The solid state structure of four ligands was determined by X-ray crystallography. The ligands bind to Cu(II) in a tridentate fashion via an (N,N,N) donor set, forming mono-ligand complexes. However, for ligands with heterocyclic morpholine and piperazine nitrogen atoms in coordination position a tetradentate binding was observed. Despite the additional coordinating donor atom, the stability of these Cu(II) complexes showed little or no increase. The Cu(II), Fe(II) and Fe(III) complexes of the studied 2-formylpyridine guanylhydrazones exhibited significantly lower stability compared to their corresponding 2-formyl or 2-acetylpyridine thiosemicarbazone analogues. The ligands underwent slow partial hydrolysis (and oxidation) in the presence of Cu(II) ions, leading to the formation of new ligands through the reorganization of structural components around the metal ion. Additionally, the studied Cu(II) complexes demonstrated a great propensity for reduction by glutathione. All these features contributed to the finding that these 2-formylpyridine guanylhydrazones and their Cu(II) complexes did not display measurable cytotoxic activity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112812"},"PeriodicalIF":3.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyin Du , Toshiyuki Kowada , EunHye Sung , Rong Liu , Andrei Soloviev , Toshitaka Matsui , Shin Mizukami
{"title":"Quantification of lysosomal labile Zn2+ and monitoring of Zn2+ efflux using a small-molecule–protein hybrid fluorescent probe","authors":"Yuyin Du , Toshiyuki Kowada , EunHye Sung , Rong Liu , Andrei Soloviev , Toshitaka Matsui , Shin Mizukami","doi":"10.1016/j.jinorgbio.2024.112811","DOIUrl":"10.1016/j.jinorgbio.2024.112811","url":null,"abstract":"<div><div>Lysosomal labile Zn<sup>2+</sup> levels have been unclear. By targeting a small-molecule fluorescent Zn<sup>2+</sup> probe, ZnDA-3H, to lysosomes via VAMP7-Halo, the lysosomal labile Zn<sup>2+</sup> concentration was determined to be 1.9 nM in HeLa cells. Furthermore, ZnDA-3H enabled direct visualization of the Zn<sup>2+</sup> efflux from the lysosomes to cytosol upon TRPMLs activation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112811"},"PeriodicalIF":3.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tarali Devi , Stefan Mebs , Dibya Jyoti Barman , Amanda Opis-Basilio , Michael Haumann , Kallol Ray
{"title":"Reinvestigation of the mechanism of dioxygen activation at a MnII(cyclam) center","authors":"Tarali Devi , Stefan Mebs , Dibya Jyoti Barman , Amanda Opis-Basilio , Michael Haumann , Kallol Ray","doi":"10.1016/j.jinorgbio.2024.112809","DOIUrl":"10.1016/j.jinorgbio.2024.112809","url":null,"abstract":"<div><div>This study deals with the unprecedented reactivity of a [(cyclam)Mn<sup>II</sup>(OTf)<sub>2</sub>] (<strong>3</strong>-<em>cis</em>; OTf = CF<sub>3</sub>SO<sub>3<sup>−</sup></sub>) with O<sub>2</sub>, which, depending on the presence or absence of a hydrogen atom donor like 1-hydroxy-2,2,6,6-tetramethyl-piperidine (TEMPO-H), selectively generates di-<em>μ</em>-oxo Mn(III)Mn(IV) (<strong>1</strong>) or Mn<sup>IV</sup><sub>2</sub> (<strong>2</strong>) complexes, respectively. Both dimers have been characterized by different techniques including single-crystal X-ray diffraction, X-ray absorption spectroscopy, and electron paramagnetic resonance. Oxygenation reactions carried out with labeled <sup>18</sup>O<sub>2</sub> and Resonance Raman spectroscopy unambiguously show that the oxygen atoms present in the Mn<sup>IV</sup>Mn<sup>III</sup> dimer originate from O<sub>2</sub>. Experimental evidences are provided for a novel method of dioxygen activation involving three Mn ions or two Mn ions and TEMPO-H to generate the bis(<em>μ</em>-oxo)dimanganese(IV) or bis(<em>μ</em>-oxo) dimanganese(III, IV) cores, respectively.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112809"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luigi F. Di Costanzo , Gianmattia Sgueglia , Carla Orlando , Maurizio Polentarutti , Linda Leone , Salvatore La Gatta , Maria De Fenza , Luca De Gioia , Angela Lombardi , Federica Arrigoni , Marco Chino
{"title":"Structural insights into temperature-dependent dynamics of METPsc1, a miniaturized electron-transfer protein","authors":"Luigi F. Di Costanzo , Gianmattia Sgueglia , Carla Orlando , Maurizio Polentarutti , Linda Leone , Salvatore La Gatta , Maria De Fenza , Luca De Gioia , Angela Lombardi , Federica Arrigoni , Marco Chino","doi":"10.1016/j.jinorgbio.2024.112810","DOIUrl":"10.1016/j.jinorgbio.2024.112810","url":null,"abstract":"<div><div>The design of protein-metal complexes is rapidly advancing, with applications spanning catalysis, sensing, and bioremediation. We report a comprehensive investigation of METPsc1, a Miniaturized Electron Transfer Protein, in complex with cadmium. This study elucidates the impact of metal coordination on protein folding and structural dynamics across temperatures from 100 K to 300 K. Our findings reveal that METPsc1, composed of two similar halves stabilized by intramolecular hydrogen bonds, exhibits a unique “clothespin-like” recoil mechanism. This allows it to adapt to metal ions of varying radii, mirroring the flexibility observed in natural rubredoxins. High-resolution crystallography and molecular dynamics simulations unveil concerted backbone motions and subtle temperature-dependent shifts in side-chain conformations, particularly for residues involved in crystal packing. Notably, Cd<img>S bond lengths increase with temperature, correlating with anisotropic motions of the sulfur atoms involved in second-shell hydrogen bonding. This suggests a dynamic role of protein matrix upon redox cycling. These insights into METPsc1 highlight its potential for catalysis and contribute to the designing of artificial metalloproteins with functional plasticity.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112810"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yajie Niu , Shuanghui Tang , Jiongbang Li , Chunxia Huang , Yan Yang , Lin Zhou , Yunjun Liu , Xiandong Zeng
{"title":"Induction of ferroptosis of iridium(III) complexes localizing at the mitochondria and lysosome by photodynamic therapy","authors":"Yajie Niu , Shuanghui Tang , Jiongbang Li , Chunxia Huang , Yan Yang , Lin Zhou , Yunjun Liu , Xiandong Zeng","doi":"10.1016/j.jinorgbio.2024.112808","DOIUrl":"10.1016/j.jinorgbio.2024.112808","url":null,"abstract":"<div><div>In this study, [Ir(ppy)<sub>2</sub>(DMHBT)](PF<sub>6</sub>) (ppy = deprotonated 1-phenylpyridine, DMHBT = 10,12-dimethylpteridino[6,7-f][1,10]phenanthroline-11,13-(10,12H)-dione, 8a), [Ir(bzq)<sub>2</sub>(DMHBT)](PF<sub>6</sub>) (bzq = deprotonated benzo[<em>h</em>]quinoline, 8b) and [Ir(piq)<sub>2</sub>(DMHBT)](PF<sub>6</sub>) (piq = deprotonated 1-phenylisoquinoline, 8c) were synthesized and characterized by HRMS, <sup>13</sup>C NMR and <sup>1</sup>H NMR. In vitro cytotoxicity experiments showed that 8a, 8b, 8c show moderate cytotoxicity against B16 cells, while the cytotoxicity of the complexes 8a, 8b and 8c toward B16 cells was greatly improved upon light irradiation, which can be used as photosensitizers to exert anticancer efficacy in photodynamic therapy (PDT). After being taken up by cells, 8a, 8b, 8c were localized in the mitochondria, resulting in a large amount of Ca<sup>2+</sup> in-flux, a burst release of ROS, a sustained opening of mitochondrial permeability transition pore, and a decrease of the mitochondrial membrane potential, which led to mitochondrial dysfunction and further activation of caspase 3 and Bcl-2 family proteins to induce apoptosis. Overloaded ROS reacted with polyunsaturated fatty acids on the cell membrane, and initiated lipid peroxidation, inhibited the x<sub>c</sub><sup>−</sup>-system-glutathione (GSH)-glutathione peroxidase 4 (GPX4) antioxidant defense system, and upregulated the expression of the damage-associated molecules, HMGB1, CRT, and HSP70. The presence of Fer-1 was effective on increasing the cell survival, which demonstrates that the complexes possess the potential to induce ferroptosis and immunogenic cell death. In addition, 8a, 8b and 8c induced autophagy by inhibiting the AKT/PI3K/mTOR signaling pathway, downregulating p62 and promoting Beclin-1 expression upon light irradiation.</div></div>","PeriodicalId":364,"journal":{"name":"Journal of Inorganic Biochemistry","volume":"264 ","pages":"Article 112808"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}