Mitochondrial Function and Dysfunction in Cancers

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (1 April 2022) | Viewed by 8358

Special Issue Editors

1. Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
2. The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Interests: mitochondria; cancer; metabolism-dysfunction-associated diseases; cell death; inflammation
Special Issues, Collections and Topics in MDPI journals
Centre Méditerranéen de Médecine Moléculaire - C3M, Université Côte d¹Azur (UCA), INSERM U1065, 151 Route de St Antoine de Ginestière, BP2 3194, 06204 Nice, France
Interests: Cancer; Hypoxia; Metabolism; Mitochondria; Primary cillium; VDAC

Special Issue Information

Dear Colleagues,

Distinct aspects of mitochondrial function and dysfunction in cancers have varied roles in different cancer stages. Many mitochondrial activities and associated pathways undergo reprogramming to support cancer cell proliferation and tumor development. Among these are: (a) Mitochondrial Dynamics: mitochondria morphological changes through fusion, fission, and mitophagy disrupted in cancer, often with a shift toward fission, to promote tumorigenesis and metastasis. (b) Mitochondrial Bioenergetics: A hallmark of cancer cells, the reprogramming of metabolism from oxidative phosphorylation (OXPHOS) to oxidative glycolysis, which is also known as the Warburg effect. (c) Mitochondrial Signaling: ROS is a common byproduct of oxidative metabolism. Cancer cells exhibit elevated mitochondrial reactive oxygen species (mROS) levels, and this can have both pro- and antitumor effects depending on the range of elevation as well as downstream pathways. (d) Mitochondrial Calcium: Ca2+ ions are important secondary messengers that extensively regulate mitochondrial functions in mROS generation, cell death, metabolism, and energy homeostasis. Cancer cells reprogram their metabolism. (e) Mitochondria-Mediated Apoptosis: Apoptosis is tightly regulated by mitochondria to maintain tissue homeostasis. Cancer cells develop strategies to resist cell death, which is considered as one of the well-established hallmarks of cancer. 

These and other mitochondrial alterations in cancer cells contribute to tumorigenesis and the development of drug resistance. Accordingly, novel approaches involving targeting mitochondria players altered in cancer have been developed for cancer therapy.

This Special Issue on “Mitochondrial Function and Dysfunction in Cancers” is expected to cover the above scope.

Based on your expertise in this field, we would like to invite you to contribute a review or full research paper for peer review and possible publication in this Special Issue: “Mitochondrial Function and Dysfunction in Cancers”.

Prof. Dr. Varda Shoshan-Barmatz
Prof. Dr. Nathalie Mazure
Guest Editors

Manuscript Submission Information

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Keywords

  • Mitochondrial dynamics
  • Mitochondrial bioenergetics
  • Mitochondrial signaling
  • Mitochondrial calcium
  • Mitochondria-mediated apoptosis

Published Papers (3 papers)

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Research

22 pages, 6120 KiB  
Article
Silencing VDAC1 to Treat Mesothelioma Cancer: Tumor Reprograming and Altering Tumor Hallmarks
by Swaroop Kumar Pandey, Renen Machlof-Cohen, Manikandan Santhanam, Anna Shteinfer-Kuzmine and Varda Shoshan-Barmatz
Biomolecules 2022, 12(7), 895; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12070895 - 27 Jun 2022
Cited by 6 | Viewed by 2826
Abstract
Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their [...] Read more.
Mesothelioma, an aggressive cancer with a poor prognosis, is linked to asbestos exposure. However, carbon nanotubes found in materials we are exposed to daily can cause mesothelioma cancer. Cancer cells reprogram their metabolism to support increased biosynthetic and energy demands required for their growth and motility. Here, we examined the effects of silencing the expression of the voltage-dependent anion channel 1 (VDAC1), controlling the metabolic and energetic crosstalk between mitochondria and the rest of the cell. We demonstrate that VDAC1 is overexpressed in mesothelioma patients; its levels increase with disease stage and are associated with low survival rates. Silencing VDAC1 expression using a specific siRNA identifying both mouse and human VDAC1 (si-m/hVDAC1-B) inhibits cell proliferation of mesothelioma cancer cells. Treatment of xenografts of human-derived H226 cells or mouse-derived AB1 cells with si-m/hVDAC1-B inhibited tumor growth and caused metabolism reprogramming, as reflected in the decreased expression of metabolism-related proteins, including glycolytic and tricarboxylic acid (-)cycle enzymes and the ATP-synthesizing enzyme. In addition, tumors depleted of VDAC1 showed altered microenvironments and inflammation, both associated with cancer progression. Finally, tumor VDAC1 silencing also eliminated cancer stem cells and induced cell differentiation to normal-like cells. The results show that silencing VDAC1 expression leads to reprogrammed metabolism and to multiple effects from tumor growth inhibition to modulation of the tumor microenvironment and inflammation, inducing differentiation of malignant cells. Thus, silencing VDAC1 is a potential therapeutic approach to treating mesothelioma. Full article
(This article belongs to the Special Issue Mitochondrial Function and Dysfunction in Cancers)
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14 pages, 1739 KiB  
Article
Sigma-1 Receptor Modulation by Ligands Coordinates Cancer Cell Energy Metabolism
by Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Rene Rost, Roland Malli and Wolfgang F. Graier
Biomolecules 2022, 12(6), 762; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12060762 - 30 May 2022
Cited by 3 | Viewed by 1908
Abstract
Sigma-1 receptor (S1R) is an important endoplasmic reticulum chaperone with various functions in health and disease. The purpose of the current work was to elucidate the involvement of S1R in cancer energy metabolism under its basal, activated, and inactivated states. For this, two [...] Read more.
Sigma-1 receptor (S1R) is an important endoplasmic reticulum chaperone with various functions in health and disease. The purpose of the current work was to elucidate the involvement of S1R in cancer energy metabolism under its basal, activated, and inactivated states. For this, two cancer cell lines that differentially express S1R were treated with S1R agonist, (+)-SKF10047, and antagonist, BD1047. The effects of the agonist and antagonist on cancer energy metabolism were studied using single-cell fluorescence microscopy analysis of real-time ion and metabolite fluxes. Our experiments revealed that S1R activation by agonist increases mitochondrial bioenergetics of cancer cells while decreasing their reliance on aerobic glycolysis. S1R antagonist did not have a major impact on mitochondrial bioenergetics of tested cell lines but increased aerobic glycolysis of S1R expressing cancer cell line. Our findings suggest that S1R plays an important role in cancer energy metabolism and that S1R ligands can serve as tools to modulate it. Full article
(This article belongs to the Special Issue Mitochondrial Function and Dysfunction in Cancers)
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21 pages, 58926 KiB  
Article
Characterization of Mitochondrial Proteome and Function in Luminal A and Basal-like Breast Cancer Subtypes Reveals Alteration in Mitochondrial Dynamics and Bioenergetics Relevant to Their Diagnosis
by Ariadna Jazmín Ortega-Lozano, Leopoldo Gómez-Caudillo, Alfredo Briones-Herrera, Omar Emiliano Aparicio-Trejo and José Pedraza-Chaverri
Biomolecules 2022, 12(3), 379; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030379 - 28 Feb 2022
Cited by 2 | Viewed by 2918
Abstract
Breast cancer (BC) is the most prevalent cancer and the one with the highest mortality among women worldwide. Although the molecular classification of BC has been a helpful tool for diagnosing and predicting the treatment of BC, developments are still being made to [...] Read more.
Breast cancer (BC) is the most prevalent cancer and the one with the highest mortality among women worldwide. Although the molecular classification of BC has been a helpful tool for diagnosing and predicting the treatment of BC, developments are still being made to improve the diagnosis and find new therapeutic targets. Mitochondrial dysfunction is a crucial feature of cancer, which can be associated with cancer aggressiveness. Although the importance of mitochondrial dynamics in cancer is well recognized, its involvement in the mitochondrial function and bioenergetics context in BC molecular subtypes has been scantly explored. In this study, we combined mitochondrial function and bioenergetics experiments in MCF7 and MDA-MB-231 cell lines with statistical and bioinformatics analyses of the mitochondrial proteome of luminal A and basal-like tumors. We demonstrate that basal-like tumors exhibit a vicious cycle between mitochondrial fusion and fission; impaired but not completely inactive mitochondrial function; and the Warburg effect, associated with decreased oxidative phosphorylation (OXPHOS) complexes I and III. Together with the results obtained in the cell lines and the mitochondrial proteome analysis, two mitochondrial signatures were proposed: one signature reflecting alterations in mitochondrial functions and a second signature exclusively of OXPHOS, which allow us to distinguish between luminal A and basal-like tumors. Full article
(This article belongs to the Special Issue Mitochondrial Function and Dysfunction in Cancers)
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