Abstract Glioblastoma (GBM) is a highly aggressive and metabolically adaptable brain tumor characterized by profound cellular heterogeneity and therapy resistance. Recent research has uncovered the phenomenon of horizontal mitochondrial transfer (HMT) between GBM cells and their microenvironment, particularly astrocytes, which contributes to tumor progression, metabolic reprogramming, and treatment resistance. This review summarises current knowledge on mitochondrial exchange in GBM via tunneling nanotubes (TNTs), tumor microtubes (TMs) and potentially via extracellular vesicles (EVs). It also explores the functional consequences of HMT, including enhanced oxidative phosphorylation (OXPHOS), increased tumorigenicity, and altered therapeutic responses. This review highlights the need for further investigation into the molecular drivers and context-specific outcomes of mitochondrial transfer in GBM, with implications for novel therapeutic strategies.
Storevik et al. (2026) studied this question.