# Mitochondria electron transport chain complexes adaptative responses to cellular stress

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $425,286

## Abstract

PROJECT SUMMARY
Radiotherapy is the most effective nonsurgical treatment for glioblastoma; however, therapeutic efficacy is
severely limited due to the development of radioresistance (RR). In the hope of overcoming this urgent clinical
problem, significant research has focused on defining the molecular mechanisms underlying RR. The overall
objective of this application is to confirm the assembly of the ETC into mitochondrial respiratory supercomplexes
(SCs) as a novel mechanism of RR. The central hypothesis of this proposal is that RR in GBM is the result of a
rearrangement of the ETC complexes into SCs triggered by the expression of COX4-1, which promotes
reprograming of glioma cell bioenergetics from predominantly aerobic glycolysis to mitochondrial oxidative
phosphorylation and, consequently, reduces the mitochondrial production of reactive oxygen species (ROS). The
specific aims proposed will use established glioma cell lines, patient-derived xenograft lines, preclinical animal
models, and patient tumor samples to rigorously assess the validity of this hypothesis. Aim 1 will determine the
role of CcO in SC assembly and mitochondrial metabolism. Aim 2 will evaluated the effects of SC on the
regulation of ROS. Aim 3 will evaluate the role of SCs in the response of IR. We expect that data generated
will vertically advance our understanding of how respiratory SCs affect outcomes in GBM and reveal the
therapeutic vulnerability in RR GBM than can be exploited by SC- disrupting agents.

## Key facts

- **NIH application ID:** 10862710
- **Project number:** 5R01NS129702-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Corinne E. Griguer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $425,286
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862710

## Citation

> US National Institutes of Health, RePORTER application 10862710, Mitochondria electron transport chain complexes adaptative responses to cellular stress (5R01NS129702-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862710. Licensed CC0.

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