Special Issue "Mitochondrial Bioenergetics in Cancer Cell Biology"

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (10 May 2018)

Special Issue Editors

Guest Editor
Prof. Dr. Alessandra Baracca

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
Website | E-Mail
Interests: cancer; metabolism; mitochondria; oxidative phosphorylation; ATP synthase; inhibitor protein IF1; hypoxia
Guest Editor
Prof. Dr. Giancarlo Solaini

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
Website | E-Mail
Interests: cancer; bioenergetics; mitochondria; hypoxia; ischemia/reperfusion; ATP synthase; inhibitor protein IF1; ROS; antioxidant molecules

Special Issue Information

Dear Colleagues,

Mitochondria are essential organelles in mammalian cells and play a key role in many processes, including oxidative phosphorylation (OXPHOS), aerobic metabolism of glucose, amino acids, and fatty acids, calcium and reactive oxygen species (ROS) homeostasis and signaling, and apoptosis. Tumor cells exhibit profound genetic, biochemical and histological differences compared to non-transformed cellular types. Many tumor cells predominantly convert glucose to lactate to generate Adenosine 5’-triphosphate (ATP) and biomass; however, glycolysis becomes the main metabolic pathway for the cell energy supply when mitochondria are impaired or when cells experience hypoxic conditions. Nonetheless, many evidence indicate the essential need of functioning mitochondria for tumor cells survival and tumor propagation.

Cancer cells have to acquire a flexible and variable metabolism to face and survive the many stress conditions such as hypoxia, low glucose and other nutrients deficiency, exposure to low pH and high ROS levels. Therefore, tumor cells have to reprogramme their metabolism at many levels and mitochondria take a pivotal part in this task, thus becoming essential to driving disease progression.

The aim of this Special Issue of Cells is to collect and publish high quality original papers, research communications, and reviews exploring the involvement of mitochondria in cancer cells metabolism adaptation particularly focusing on bioenergetics.

Prof. Dr. Alessandra Baracca
Prof. Dr. Giancarlo Solaini
Guest Editors

Manuscript Submission Information

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Keywords

  • transport
  • oxidative phosphorylation
  • respiratory chain complexes
  • ATP synthase
  • reactive oxygen/nitrogen species
  • redox biology
  • metabolism reprogramming
  • metabolism regulation
  • aminoacids metabolism
  • fatty acids metabolism
  • pyruvate/lactate metabolism
  • hypoxia
  • mitochondria-related signaling pathway
  • tumor
  • anti-tumor drug

Published Papers (4 papers)

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Research

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Open AccessFeature PaperArticle Hypoxia and IF1 Expression Promote ROS Decrease in Cancer Cells
Received: 25 May 2018 / Revised: 15 June 2018 / Accepted: 19 June 2018 / Published: 21 June 2018
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Abstract
The role of reactive oxygen species (ROS) in the metabolic reprogramming of cells adapted to hypoxia and the interplay between ROS and hypoxia in malignancy is under debate. Here, we examined how ROS levels are modulated by hypoxia in human cancer compared to
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The role of reactive oxygen species (ROS) in the metabolic reprogramming of cells adapted to hypoxia and the interplay between ROS and hypoxia in malignancy is under debate. Here, we examined how ROS levels are modulated by hypoxia in human cancer compared to untransformed cells. Short time exposure (20 min) of either fibroblasts or 143B osteosarcoma cells to low oxygen tension down to 0.5% induced a significant decrease of the cellular ROS level, as detected by the CellROX fluorescent probe (−70%). Prolonging the cells’ exposure to hypoxia for 24 h, ROS decreased further, reaching nearly 20% of the normoxic value. In this regard, due to the debated role of the endogenous inhibitor protein (IF1) of the ATP synthase complex in cancer cell bioenergetics, we investigated whether IF1 is involved in the control of ROS generation under severe hypoxic conditions. A significant ROS content decrease was observed in hypoxia in both IF1-expressing and IF1- silenced cells compared to normoxia. However, IF1-silenced cells showed higher ROS levels compared to IF1-containing cells. In addition, the MitoSOX Red-measured superoxide level of all the hypoxic cells was significantly lower compared to normoxia; however, the decrease was milder than the marked drop of ROS content. Accordingly, the difference between IF1-expressing and IF1-silenced cells was smaller but significant in both normoxia and hypoxia. In conclusion, the interplay between ROS and hypoxia and its modulation by IF1 have to be taken into account to develop therapeutic strategies against cancer. Full article
(This article belongs to the Special Issue Mitochondrial Bioenergetics in Cancer Cell Biology)
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Open AccessArticle Alterations of Oxidative Phosphorylation Complexes in Papillary Thyroid Carcinoma
Received: 9 April 2018 / Revised: 3 May 2018 / Accepted: 7 May 2018 / Published: 9 May 2018
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Abstract
The papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with disruptive mutations in mitochondrial complex I subunits reported at very low frequency. Furthermore, metabolic diversity of PTC has been postulated owing to variable messenger RNA (mRNA) expression
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The papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland, with disruptive mutations in mitochondrial complex I subunits reported at very low frequency. Furthermore, metabolic diversity of PTC has been postulated owing to variable messenger RNA (mRNA) expression of genes encoding subunits of the oxidative phosphorylation (OXHPOS) complexes. The aim of the present study was to evaluate the metabolic diversity of the OXPHOS system at the protein level by using immunohistochemical staining. Analysis of 18 human PTCs revealed elevated mitochondrial biogenesis but significantly lower levels of OXPHOS complex I in the tumor tissue (p < 0.0001) compared to the adjacent normal tissue. In contrast, OXPHOS complexes II–V were increased in the majority of PTCs. In three PTCs, we found pathologic mutations within mitochondrially encoded complex I subunits. Our data indicate that PTCs are characterized by an oncocytic metabolic signature that is in low complex I is combined with elevated mitochondrial mass and high complex II–V levels, which might be an important factor for tumor formation. Full article
(This article belongs to the Special Issue Mitochondrial Bioenergetics in Cancer Cell Biology)
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Review

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Open AccessReview The Nutrient-Sensing Hexosamine Biosynthetic Pathway as the Hub of Cancer Metabolic Rewiring
Received: 30 April 2018 / Revised: 29 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
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Abstract
Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP).
[...] Read more.
Alterations in glucose and glutamine utilizing pathways and in fatty acid metabolism are currently considered the most significant and prevalent metabolic changes observed in almost all types of tumors. Glucose, glutamine and fatty acids are the substrates for the hexosamine biosynthetic pathway (HBP). This metabolic pathway generates the “sensing molecule” UDP-N-Acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is the substrate for the enzymes involved in protein N- and O-glycosylation, two important post-translational modifications (PTMs) identified in several proteins localized in the extracellular space, on the cell membrane and in the cytoplasm, nucleus and mitochondria. Since protein glycosylation controls several key aspects of cell physiology, aberrant protein glycosylation has been associated with different human diseases, including cancer. Here we review recent evidence indicating the tight association between the HBP flux and cell metabolism, with particular emphasis on the post-transcriptional and transcriptional mechanisms regulated by the HBP that may cause the metabolic rewiring observed in cancer. We describe the implications of both protein O- and N-glycosylation in cancer cell metabolism and bioenergetics; focusing our attention on the effect of these PTMs on nutrient transport and on the transcriptional regulation and function of cancer-specific metabolic pathways. Full article
(This article belongs to the Special Issue Mitochondrial Bioenergetics in Cancer Cell Biology)
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Open AccessReview Experimental Methods for Studying Cellular Heme Signaling
Received: 23 April 2018 / Revised: 15 May 2018 / Accepted: 18 May 2018 / Published: 24 May 2018
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Abstract
The study of heme is important to our understanding of cellular bioenergetics, especially in cancer cells. The function of heme as a prosthetic group in proteins such as cytochromes is now well-documented. Less is known, however, about its role as a regulator of
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The study of heme is important to our understanding of cellular bioenergetics, especially in cancer cells. The function of heme as a prosthetic group in proteins such as cytochromes is now well-documented. Less is known, however, about its role as a regulator of metabolic and energetic pathways. This is due in part to some inherent difficulties in studying heme. Due to its slightly amphiphilic nature, heme is a “sticky” molecule which can easily bind non-specifically to proteins. In addition, heme tends to dimerize, oxidize, and aggregate in purely aqueous solutions; therefore, there are constraints on buffer composition and concentrations. Despite these difficulties, our knowledge of heme’s regulatory role continues to grow. This review sums up the latest methods used to study reversible heme binding. Heme-regulated proteins will also be reviewed, as well as a system for imaging the cellular localization of heme. Full article
(This article belongs to the Special Issue Mitochondrial Bioenergetics in Cancer Cell Biology)
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