Mitochondrial supercomplex‐associated proximity increases in malignant glioma tissue
Author(s)
Type
Journal Article
Abstract
In rapidly growing tumors, including gliomas, heterogeneous microenvironments with fluctuating oxygen and nutrient availability impose strong selective pressure for metabolic adaptation. For over a century, mitochondria have been recognized as central to the reprogramming of cancer metabolism. However, it remains unclear whether and how remodeling of oxidative phosphorylation (OXPHOS), including organization of electron transport chain (ETC) complexes, contributes to the proliferation of cancer cells. Recent reports suggest that mitochondrial supercomplexes (SCs), higher-order assemblies of ETC complexes, are enriched in tumor cells and may support proliferation by increasing respiratory efficiency and stabilizing electron transfer. Here, we evaluated respiratory SC formation across glioma grades by quantifying ETC complex proximity within mitochondria in patient tissue using proximity ligation assay (PLA). We observed increased PLA signal between ETC complexes I and IV, consistent with increased respirasome assembly, that was associated with malignant glioma (Grades III and IV), and increased proximity between ETC Complexes III and IV that was most prominent in proliferating glioblastoma (Grade IV) cells. Although the precise functions of SCs remain debated, these increases in high-grade glioma relative to Grade II and control tissue suggest that SC remodeling may be a feature of malignant glioma metabolic remodeling.
Date Issued
2026-10-31
Date Acceptance
2026-09-29
Citation
The FASEB Journal, 2026, 40 (20)
ISSN
0892-6638
Publisher
Wiley
Journal / Book Title
The FASEB Journal
Volume
40
Issue
20
Copyright Statement
© 2026 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Article Number
e72363
Date Publish Online
2026-10-13