{
  "id": 13139130,
  "title": "A membrane-disruptive action of VBIT-4 challenges its role as a widely used VDAC1 oligomerization inhibitor",
  "url": "https://urgent.news/2026/10/09/a-membrane-disruptive-action-of-vbit-4-challenges-its-role-as-a",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-09T00:00:00.000Z",
  "source": {
    "name": "eLife",
    "slug": "elife",
    "url": "https://elifesciences.org/articles/111980"
  },
  "original_language": "en",
  "account": "Voltage-dependent anion channel (VDAC) is a crucial component of the mitochondrial outer membrane, facilitating the exchange of metabolites and maintaining mitochondrial function. VDAC1 oligomerization has been believed to regulate processes like mitochondrial DNA release and membrane remodeling; however, the exact mechanisms involved are not entirely clear. VBIT-4 has been commonly employed as a potential inhibitor of VDAC1 oligomerization, even though there is a lack of solid evidence supporting this claim. To gain a better understanding of VBIT-4's function, researchers utilized high-speed atomic force microscopy (AFM) to study the behavior of VDAC1 assemblies within lipid membranes and to assess the impact of VBIT-4.\n\nSurprisingly, the findings revealed that VBIT-4 induced detrimental membrane defects and permeabilization at micromolar concentrations, regardless of its interaction with VDAC1. Through quantitative AFM analysis, it was determined that VBIT-4 does not alter the organization of VDAC1 clusters. In order to further comprehend VBIT-4's mechanism of action, complementary studies were conducted, including electrophysiology, microscale thermophoresis, and coarse-grained molecular dynamics simulations. These investigations demonstrated that VBIT-4 integrates into lipid bilayers, increases membrane permeability, and destabilizes membrane structure without affecting VDAC1 channel properties or assemblies.\n\nThe implications of these findings are significant, as they suggest that VBIT-4 does not function as a specific inhibitor of VDAC1 oligomerization but rather behaves as a membrane-active compound. This new perspective on VBIT-4's role challenges previous assumptions and emphasizes the necessity of thoroughly evaluating drug-membrane interactions when targeting membrane proteins. By reconsidering the effects of VBIT-4, researchers can refine their understanding of studies involving this compound and refine their approaches to targeting mitochondrial proteins more effectively.",
  "summary": "Voltage-dependent anion channel (VDAC) is the most abundant protein of the mitochondrial outer membrane and a key regulator of metabolite exchange and mitochondrial physiology. Its oligomerization has been proposed to control processes such as mitochondrial DNA release and membrane remodeling, yet the underlying mechanisms remain poorly defined. VBIT-4 has been widely used as a putative inhibitor…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}