Document Type

Article

Publication Date

2026

Publication Title

Onco

Volume

6

Issue

1

Pages

16

DOI

10.3390/onco6010016

Abstract

Background/Objectives: Chondrosarcoma, glioblastoma, acute myeloid leukemia, chronic lymphocytic leukemia, and cholangiocarcinoma cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme metabolizes alpha-ketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers, leading to altered cellular metabolism. Emerging evidence suggests that mitochondrial transfer between cancer and recipient cells represents an important form of intercellular communication that may influence cellular metabolism. The presence of intercellular TNTs between IDH2-mutant chondrosarcoma cells motivated an investigation into mitochondria-associated physiological changes occurring during an intercellular exchange with immune cells. A mitochondrial transfer is a two-way process, and we hypothesized that mitochondria-associated material derived from IDH2-mutant chondrosarcoma cells is exchanged with normal cells through TNTs. We further hypothesized that disruption of the actin cytoskeleton will inhibit this transfer. Accordingly, our objectives were to (1) quantify the extent and directionality of the mitochondrial exchange between IDH2-mutant cells and wild-type cells and to modulate this process via cytoskeletal inhibitors, and (2) measure the metabolic changes associated with the coculture and mitochondrial exchange. Methods: IDH2-mutant chondrosarcoma cells were cocultured with immune cells in vitro to quantify the extent and directionality of the mitochondrial exchange, and cytochalasin B was used as a cytoskeletal inhibitor to disrupt actin-dependent transfer. Metabolic changes associated with coculture and mitochondrial exchange were assessed using Seahorse extracellular flux analysis. Results: The experimental data presented here demonstrate a bidirectional exchange of mitochondria-associated material between IDH2-mutant chondrosarcoma cells and immune cells in vitro, accompanied by metabolic alterations in both cell types. Conclusions: These findings advance our understanding of intercellular communication in the tumor microenvironment and provide a foundation for future studies examining the functional and therapeutic relevance of a mitochondrial exchange in IDH2-mutant cancers.

Rights

© 2026 by the authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "The data used and or analyzed during the current study are available from the corresponding author upon reasonable request."

Original Publication Citation

Wyckoff, C., Osgood, C., Jing, E., & Stacey, M. (2026). Metabolic reprogramming following mitochondrial transfer between IDH2-mutant chondrosarcoma cells and a normal B-cell line. Onco, 6(1), Article 16. https://doi.org/10.3390/onco6010016

ORCID

0009-0000-6140-2095 (Wyckoff), 0009-0001-8330-2703 (Osgood), 0000-0002-3807-6233 (Stacey)

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