Table of Content

Mitochondrial Signaling and Metabolism in Cancer

Submission Deadline: 01 August 2022 (closed)

Guest Editors

Dr. Tasleem Arif, Department of Cell, Developmental & Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, USA.


Cancer is a complicated disease with several genetic, epigenomic, transcriptomic, proteomic, and metabolic abnormalities. Otto Warburg described the altered metabolism of cancer cells in 1924, demonstrating that they anaerobically consume glucose, followed by an increase in lactate production. Lactate promotes the survival and growth of cancer cells in the tumor microenvironment. Cancer cells' altered metabolism is recognized as a critical characteristic of cancer since it regulates cancer growth and invasion-related activities. Metabolic reprogramming is required for cancer cell survival in hypoxia, for immune monitoring of cancer cells, and for fast cell multiplication, which enhances tumor cells' biological activity.

Notably, cancer cell plasticity necessitates frequent changes in cellular metabolism and immune system activation to maintain a balance between tumor development and expansion. While it is well established that this confers growth benefits on the tumor, the intracellular interplay underlying these alterations remains unknown. The mitochondria are critical regulators of this process.

Mitochondria are organelles that are involved in bioenergy production, biosynthesis, and signaling. Mitochondrial signaling is critical for recognizing and responding to cellular stress. As a result, mitochondrial function and signaling are thought to be important modulators of carcinogenesis and cancer therapy. Additionally, they are crucial to immunity. Indeed, mitochondria may serve as a platform for the activation of innate immunity signaling through the mitochondrial antiviral–signaling protein (MAVS) located on their outer membrane. Simultaneously, since mitochondria are the primary source of reactive oxygen species (ROS), mitochondrial DNA (mtDNA) is continually subjected to oxidative stress, which results in a steady buildup of detrimental mutations if not addressed. This eventually results in mitochondrial malfunction and the release of mtDNA into the cytosol, where it behaves as a danger-associated molecular pattern (DAMP), activating important innate immune signaling pathways such as TLR9 and cGAS/STING. Mitochondrial metabolic inefficiency caused by mtDNA mutations has been reported in a variety of malignancies and is strongly linked with a poor prognosis in patients.

This Special Issue will cover a variety of topics related to next-generation cancer therapies and the mitochondrial function pathway in cancer formation and progression. A better knowledge of mitochondrial metabolic dysfunction and signaling will shed light on a critical aspect of tumor cell biology and may possibly uncover potential therapeutic targets.


Mitochondria, Cancer Cell, Metabolism, Signaling, Mtdna, ROS, Mitochondrial Dysfunction, Metabolic Pathways, Inflammation, Therapy Targets

Published Papers

  • Open Access


    Anti-cancer effects of sitagliptin, vildagliptin, and exendin-4 on triple-negative breast cancer cells via mitochondrial modulation

    BIOCELL, Vol.46, No.12, pp. 2645-2657, 2022, DOI:10.32604/biocell.2022.021754
    (This article belongs to this Special Issue: Mitochondrial Signaling and Metabolism in Cancer)
    Abstract Triple-negative breast cancer (TNBC) cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria. On the other hand, dipeptidyl peptidase-IV (DPP-IV) inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis, but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line. We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase (AMPK), which activates the downstream transcription factors PGC-1α, PGC-1β, or FOXO1 for mitochondrial biogenesis; above-mentioned incretin-based therapies are also known to… More >

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