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Cited by 2Cancer, Hypoxia, and MetabolismMitochondrial Function and PathologyMetabolism, Diabetes, and Cancer

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Alteration of metabolic activity regulates mitochondrial temperature in diagnosis in HepG2 hepatocellular carcinoma cells

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Gaser, Ola A., Nasr, Mohamed A., Hussein, Alaa E., Salah, Radwa Ayman, Saad, Shams M., Ehab, Seif, Aboomar, Nourhan M., Elmehrath, Ahmed O., Salah, Ayman, Chang, Young-Tae, Hedrick, Mal, Castanedo, Lázaro A. M., Fahimi, Peyman, Matta, Chérif F., El-Badri, Nagwa·2025·Scientific Reports
DOI 10.1038/s41598-025-02807-0PMC PMC12638863
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Abstract

Oxidative phosphorylation (OXPHOS) is a key player in mitochondrial bioenergetic functions. In hepatocellular carcinoma (HCC), OXPHOS slows down or switches to glycolysis via what is known as the Warburg effect. The altered respiration in cancer was reported to affect mitochondrial temperature. We investigated the impact of the metabolic switch on the mitochondrial temperature in HepG2 HCC cell line. Metformin (N, N-dimethylbiguanide) treatment was used to suppress glycolysis to emulate lower metabolically active cells (Met-HepG2). The mitochondrial temperature was assessed using mito-thermo yellow (MTY) absorbing mitochondrial radiant heat. Mito-tracker green (MTG) fluorescent dye was used to confirm mitochondrial localization. Our data showed lower MTY dye intensity in the Met-HepG2 treated group, indicating a significant increase in mitochondrial temperature compared to untreated HepG2 cells (NT-HepG2). Genotypic analysis of the metabolic respiration gene expression showed significant down-regulation in glycolytic genes (ERR-gamma, HK2, PGK, ALDOC, TPI1, IDH1, and PKM2) in the Met-HepG2 cells compared to the NT-HepG2 cells. OXPHOS as evidenced by ATP, ROS, and NADPH production was significantly up-regulated in the Met-HepG2 group compared to the NT-HepG2 group. Transmission electron microscopy showed fewer mitochondria with swollen elongated appearance, as a marker for activated OXPHOS in the Met-HepG2 group. These data show a correlation between HepG2 altered metabolism and mitochondrial temperature and suggest that less metabolically active HepG2 cells are correlated with higher mitochondrial temperature, providing evidence for a possible role of mitochondrial temperature in diagnosis of HCC.

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Metadata

Authors
Gaser, O. A., Nasr, M. A., Hussein, A. E., Salah, R. A., Saad, S. M., Ehab, S., Aboomar, N. M., Elmehrath, A. O., Salah, A., Chang, Y.-T., Hedrick, M., Castanedo, L. A. M., Fahimi, P., Matta, C. F., & El-Badri, N.
Affiliations
  • Zewail City of Science and Technology (EG)
  • Cairo University (EG)
  • Pohang University of Science and Technology (KR)
  • Mount Saint Vincent University (CA)
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2025-11-21
Volume
15
Issue
1
Pages
41155-41155
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-025-02807-0
PMC
PMC12638863
OpenAlex
W4416442151
Cited by
2
References
87
Citations by year
2026: 1 · 2025: 1
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Basic Science Research Institute (2021R1A6A1A10042944)
  • Korea government (2023R1A2C300453411)
  • The Academy of Scientific Research & Technology (JESOR #5275)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
hepatocellular carcinoma, oxidative phosphorylation, Warburg effect, metabolic switch, glycolysis, metformin, HepG2 cells, glycolytic gene expression, mitochondrial respiration, cancer diagnosis
MeSH terms
Glycolysis, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Metformin, Mitochondria, Oxidative Phosphorylation, Temperature, Gene Expression Regulation, Neoplastic, Reactive Oxygen Species, Hep G2 Cells

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