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Mitochondrial Respiration and Energy Metabolism in Cancer Cells
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Mitochondrial Respiration and Energy Metabolism in Cancer Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 3848

Special Issue Editor

Prof. Dr. Rasa Banienė

E-Mail Website
Guest Editor
Biochemistry Department, Lithuanian University of Health Sciences, Kaunas, Lithuania
Interests: mitochondrial functions

Special Issue Information

Dear Colleagues,

Mitochondria are intracellular organelles involved in energy production, cell metabolism and cell signaling and consume over 95% of all oxygen that reaches our cells in order to produce ATP through oxidative phosphorylation. Mitochondria are essential not only in the process of energetic ATP synthesis but also in lipid metabolism, amino acid metabolism, the TCA cycle, and nucleic acid metabolism. Mitochondria have their own mitochondrial DNA. Mutations in mtDNA and in the nuclear genes encoding mitochondrial proteins (TCA cycle, respiratory chain complexes) are commonly observed in cancer cells and are involved in cancer metabolism remodeling. Moreover, mitochondria play critical roles in many physiological processes, such as apoptosis and redox or calcium homeostasis and produce large amounts of reactive oxygen species (ROS) that can contribute to oxidative stress and potentially promote cancer development. Dysfunctional mitochondria can lead to metabolic reprogramming in cancer cells, allowing them to meet the increased energy demands associated with rapid proliferation. For energy, cancer cells utilize glycolysis preferentially over mitochondrial oxidative phosphorylation even in aerobic circumstances, also called the Warburg effect. Decreased cellular respiration due to hypoxia and increased ROS could affect cancer cell proliferation. The regulatory mechanisms leading to decreased cellular respiration in cancer cells are complicated and may depend on tumor type.

Prof. Dr. Rasa Banienė
Guest Editor

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Keywords

  • mitochondria
  • respiration
  • cancer
  • ATP synthesis
  • mtDNA
  • oxidative stress
  • glycolysis
  • cell death

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Published Papers (3 papers)

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23 pages, 8886 KiB  
Article
Multicore, SDS-Based Polyelectrolyte Nanocapsules as Novel Nanocarriers for Paclitaxel to Reduce Cardiotoxicity by Protecting the Mitochondria
by Marzena Szwed, Anastazja Poczta-Krawczyk, Katarzyna D. Kania, Kacper Wiktorowski, Kamila Podsiadło, Agnieszka Marczak and Krzysztof Szczepanowicz
Int. J. Mol. Sci. 2025, 26(3), 901; https://doi.org/10.3390/ijms26030901 - 22 Jan 2025
Viewed by 904
Abstract
The clinical application of paclitaxel (PTX), a widely used anticancer drug, is constrained by cardiac arrhythmias and disruptions in vascular homeostasis. To mitigate the non-specific, high toxicity of PTX towards cardiomyocytes, we propose the application of newly synthesized SDS-based polyelectrolyte multicore nanocapsules. This [...] Read more.
The clinical application of paclitaxel (PTX), a widely used anticancer drug, is constrained by cardiac arrhythmias and disruptions in vascular homeostasis. To mitigate the non-specific, high toxicity of PTX towards cardiomyocytes, we propose the application of newly synthesized SDS-based polyelectrolyte multicore nanocapsules. This study aims to verify the hypothesis that SDS-based NCs can mitigate the cytotoxic effects of PTX on cardiac cells and serve as effective nanocarriers for this drug. We investigated two types of multicore NCs with differing polyelectrolyte coatings: poly-L-lysine (PLL) and a combination of PLL with poly-L-glutamic acid (PGA). The cytotoxicity of the formulated nanosystems was evaluated using HL-1 cardiomyocytes. Oxygraphy, flow cytometry, spectrophotometry, spectrofluorimetry, fluorescence microscopy, and RT-PCR were employed to assess disruptions in cardiac cellular homeostasis. Our data revealed that, among the tested NCs, SDS/PLL/PGA/PTX exhibited reduced cardiotoxicity and were better tolerated by HL−1 cardiomyocytes compared to SDS/PLL/PTX or PTX alone. In addition, SDS/PLL/PGA/PTX showed a marginal disruption of mitochondria’s homeostasis, and no changes in APT level and intracellular calcium concentrations were observed. These findings underscore the potential of SDS-based multicore nanocarriers in anticancer therapy, particularly due to diminished cardiotoxicity and long-term stability in the biological fluids. Full article
(This article belongs to the Special Issue Mitochondrial Respiration and Energy Metabolism in Cancer Cells)
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21 pages, 2400 KiB  
Article
Exploring Aerobic Energy Metabolism in Breast Cancer: A Mutational Profile of Glycolysis and Oxidative Phosphorylation
by Ricardo Cunha de Oliveira, Giovanna C. Cavalcante and Giordano B. Soares-Souza
Int. J. Mol. Sci. 2024, 25(23), 12585; https://doi.org/10.3390/ijms252312585 - 23 Nov 2024
Cited by 2 | Viewed by 1320
Abstract
Energy metabolism is a fundamental aspect of the aggressiveness and invasiveness of breast cancer (BC), the neoplasm that most affects women worldwide. Nonetheless, the impact of genetic somatic mutations on glycolysis and oxidative phosphorylation (OXPHOS) genes in BC remains unclear. To fill these [...] Read more.
Energy metabolism is a fundamental aspect of the aggressiveness and invasiveness of breast cancer (BC), the neoplasm that most affects women worldwide. Nonetheless, the impact of genetic somatic mutations on glycolysis and oxidative phosphorylation (OXPHOS) genes in BC remains unclear. To fill these gaps, the mutational profiles of 205 screened genes related to glycolysis and OXPHOS in 968 individuals with BC from The Cancer Genome Atlas (TCGA) project were performed. We carried out analyses to characterize the mutational profile of BC, assess the clonality of tumors, identify somatic mutation co-occurrence, and predict the pathogenicity of these alterations. In total, 408 mutations in 132 genes related to the glycolysis and OXPHOS pathways were detected. The PGK1, PC, PCK1, HK1, DONSON, GPD1, NDUFS1, and FOXRED1 genes are also associated with the tumorigenesis process in other types of cancer, as are the genes BRCA1, BRCA2, and HMCN1, which had been previously described as oncogenes in BC, with whom the target genes of this work were associated. Seven mutations were identified and highlighted due to the high pathogenicity, which are present in more than one of our results and are documented in the literature as being correlated with other diseases. These mutations are rs267606829 (FOXRED1), COSV53860306 (HK1), rs201634181 (NDUFS1), rs774052186 (DONSON), rs119103242 (PC), rs1436643226 (PC), and rs104894677 (ETFB). They could be further investigated as potential biomarkers for diagnosis, prognosis, and treatment of BC patients. Full article
(This article belongs to the Special Issue Mitochondrial Respiration and Energy Metabolism in Cancer Cells)
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Other

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13 pages, 2075 KiB  
Protocol
Optimised Workflows for Profiling the Metabolic Fluxes in Suspension vs. Adherent Cancer Cells via Seahorse Technology
by Eugenia Giglio, Martina Giuseffi, Simona Picerno, Marzia Sichetti and Marisabel Mecca
Int. J. Mol. Sci. 2025, 26(1), 154; https://doi.org/10.3390/ijms26010154 - 27 Dec 2024
Viewed by 1046
Abstract
Oxidative phosphorylation and glycolysis are the main ATP-generating pathways in cell metabolism. The balance between these two pathways is frequently altered to carry out cell-specific activities in response to stimuli involving activation, proliferation, or differentiation. Despite being a useful tool for researching metabolic [...] Read more.
Oxidative phosphorylation and glycolysis are the main ATP-generating pathways in cell metabolism. The balance between these two pathways is frequently altered to carry out cell-specific activities in response to stimuli involving activation, proliferation, or differentiation. Despite being a useful tool for researching metabolic profiles in real time in relatively small numbers of cancer cells, the main Agilent Seahorse XF Pro Analyzer (Agilent Technologies, Santa Clara, CA, USA) guideline is currently not fully detailed in the distinction between suspensions vs. adherent cancer cells. This article provides step-by-step protocols for profiling metabolic fluxes in suspension vs. adherent cancer cells via Seahorse technology, including adjustments for normalisation of data on the basis of the number of viable cells or the total protein content. Owing to the adaptations of plates, reagents, cell count, and protein quantification, it is possible to (i) analyse both adherent and suspension cells with a single instrument; (ii) conduct all experiments in 96-well plates, thus using fewer cells, media, and reagents; (iii) determine the effect of a drug or compound directly on cell metabolism; (iv) normalise data on the basis of the number of viable cells or the total protein content via a spectrophotometer; and (v) achieve notable savings in cost and time. Full article
(This article belongs to the Special Issue Mitochondrial Respiration and Energy Metabolism in Cancer Cells)
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