{"title":"Melittin-induced modulation of mitochondrial physiology: Beyond the antitumoral actions","authors":"Marcos Roberto de Oliveira","doi":"10.1016/j.toxicon.2025.108555","DOIUrl":null,"url":null,"abstract":"<div><div>Melittin (MEL), a cationic amphipathic peptide derived from bee venom, exhibits dual roles in mitochondrial physiology, with both cytoprotective and cytotoxic outcomes. This review synthesizes current findings on MEL-induced modulation of mitochondrial pathways in normal and cancer cells. Beyond its well-documented roles in apoptosis regulation, MEL influences mitochondrial function by altering membrane potential, regulating respiratory chain activity, and impacting ATP production. These effects are context-dependent and vary across normal and tumor cell models. MEL can attenuate mitochondrial dysfunction by preserving mitochondrial membrane integrity and reducing reactive oxygen species, while in cancer cells, it often promotes mitochondrial depolarization, cytochrome <em>c</em> release, and caspase activation, culminating in intrinsic apoptotic signaling. Importantly, MEL modulates the expression of key proteins such as BAX, BCL-2, and APAF-1, and interacts with signaling cascades including PI3K/Akt, NF-κB, MAPKs, and Nrf2/HO-1. Recent studies have demonstrated that MEL also regulates mitochondrial quality control mechanisms, including the stimulation of mitophagy through PINK1/Parkin and AMPK-related pathways. Moreover, MEL interacts directly with mitochondrial membranes and affects enzymes critical for energy metabolism, such as F1-ATPase, contributing to altered bioenergetic output. These actions suggest that MEL's mitochondrial effects extend beyond cell death regulation, encompassing broader control over metabolic activity, oxidative stress, and organelle maintenance. Future investigations should integrate redox biology, bioenergetics, and mitochondrial signaling to optimize MEL's therapeutic applications. Altogether, MEL represents a unique modulator of mitochondrial health, whose dual actions necessitate rigorous contextual evaluation for clinical translation.</div></div>","PeriodicalId":23289,"journal":{"name":"Toxicon","volume":"266 ","pages":"Article 108555"},"PeriodicalIF":2.4000,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicon","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041010125003307","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Melittin (MEL), a cationic amphipathic peptide derived from bee venom, exhibits dual roles in mitochondrial physiology, with both cytoprotective and cytotoxic outcomes. This review synthesizes current findings on MEL-induced modulation of mitochondrial pathways in normal and cancer cells. Beyond its well-documented roles in apoptosis regulation, MEL influences mitochondrial function by altering membrane potential, regulating respiratory chain activity, and impacting ATP production. These effects are context-dependent and vary across normal and tumor cell models. MEL can attenuate mitochondrial dysfunction by preserving mitochondrial membrane integrity and reducing reactive oxygen species, while in cancer cells, it often promotes mitochondrial depolarization, cytochrome c release, and caspase activation, culminating in intrinsic apoptotic signaling. Importantly, MEL modulates the expression of key proteins such as BAX, BCL-2, and APAF-1, and interacts with signaling cascades including PI3K/Akt, NF-κB, MAPKs, and Nrf2/HO-1. Recent studies have demonstrated that MEL also regulates mitochondrial quality control mechanisms, including the stimulation of mitophagy through PINK1/Parkin and AMPK-related pathways. Moreover, MEL interacts directly with mitochondrial membranes and affects enzymes critical for energy metabolism, such as F1-ATPase, contributing to altered bioenergetic output. These actions suggest that MEL's mitochondrial effects extend beyond cell death regulation, encompassing broader control over metabolic activity, oxidative stress, and organelle maintenance. Future investigations should integrate redox biology, bioenergetics, and mitochondrial signaling to optimize MEL's therapeutic applications. Altogether, MEL represents a unique modulator of mitochondrial health, whose dual actions necessitate rigorous contextual evaluation for clinical translation.
期刊介绍:
Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee.
Toxicon''s "aims and scope" are to publish:
-articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms
-papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins
-molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins
-clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained.
-material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems.
-articles on the translational application of toxins, for example as drugs and insecticides
-epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged.
-articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon.
-review articles on problems related to toxinology.
To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.