Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription

The Warburg effect has long suggested that oxidative phosphorylation (OXPHOS) is dispensable for tumor growth. However, recent studies have shown that the mitochondrial RNA polymerase inhibitors IMT1 and IMT1b, which impair OXPHOS, are potent anticancer agents. Here, we demonstrate that ionomycin, a selective ionophore known to modulate mitochondrial homeostasis, similarly inhibits mitochondrial gene expression across cancer cell lines. Specifically, gene expression and nascent RNA profiling revealed a global downregulation of mitochondrial gene transcription in Jurkat T, THP-1, HeLa, and NCI-H441 cells. Thus, we conclude that ionomycin suppressed mitochondrial gene transcription, impaired OXPHOS, and thereby inhibited cancer cell proliferation and growth, providing a novel insight into the function of ionomycin.

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Publication Details

Journal
FEBS Open Bio
Published
2026-09-01
DOI
https://doi.org/10.1002/2211-5463.70297
Primary Topic
Mitochondrial Function and Pathology
Type
article
Field-Weighted Citation Impact
0.00

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article

Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription

Chuanman Zhou, Mingqiang Deng, Lishen Wang, 朱登勇 et al.
FEBS Open Bio
Mitochondrial Function and Pathology
article

Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription

Chuanman Zhou, Mingqiang Deng, Lishen Wang, 朱登勇, Xichen Bao, Dongjun Liu, Menghui Yin, Zhenhua Zhang, Diqin Lai, Peng Tang, Dongmei He
article en

Abstract

The Warburg effect has long suggested that oxidative phosphorylation (OXPHOS) is dispensable for tumor growth. However, recent studies have shown that the mitochondrial RNA polymerase inhibitors IMT1 and IMT1b, which impair OXPHOS, are potent anticancer agents. Here, we demonstrate that ionomycin, a selective ionophore known to modulate mitochondrial homeostasis, similarly inhibits mitochondrial gene expression across cancer cell lines. Specifically, gene expression and nascent RNA profiling revealed a global downregulation of mitochondrial gene transcription in Jurkat T, THP-1, HeLa, and NCI-H441 cells. Thus, we conclude that ionomycin suppressed mitochondrial gene transcription, impaired OXPHOS, and thereby inhibited cancer cell proliferation and growth, providing a novel insight into the function of ionomycin.

FEBS Open Bio
Guangzhou Institutes of Biomedicine and Health (CN), Guangzhou Automobile Group (China) (CN), Shandong First Medical University (CN), University of Chinese Academy of Sciences (CN), Guangzhou Medical University (CN)
State Key Laboratory of Respiratory Disease, National Natural Science Foundation of China, Chinese Academy of Sciences, National Key Research and Development Program of China, Science and Technology Planning Project of Guangdong Province, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Basic and Applied Basic Research Foundation of Guangdong Province, Chinese Polar Environment Comprehensive Investigation and Assessment Programmes
Good health and well-being
Openalex Percentile: Top 23%
Mitochondrial Function and Pathology
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