Mitochondrial Metabolism and Signaling in Cancer

Dear Colleagues,

Cancer is a multifaceted illness in which genomic, epigenomic, transcriptomic, proteomic, or metabolic disorders have many modifications.

In 1924, Otto Warburg characterized the altered metabolism of cancer cells, which anaerobically metabolize glucose, with an accompanied rise in the synthesis of lactate. Lactate supports cancer cell survival, and its development, in the tumor microenvironment. The altered metabolism of cancer cells is regarded as the vital feature of cancer since it governs cancer progression and invasion-related activities. Metabolic reprogramming is essential for cancer cell survival in tumor hypoxia, for cancer immune surveillance, and to support rapid cell proliferation enhancing tumor cells’ biological activities.

Of note, cancer cell plasticity requires rapid changes in cellular metabolism and the activation of the immune system, to balance tumor growth and expansion. While this is known to confer growth advantages to the tumor, intracellular crosstalks underlying these changes remain poorly understood. Key players in this regulation are the mitochondria.

Mitochondria are organelles of bioenergy, biosynthesis, and signaling. Mitochondrial signaling is crucial in sensing cellular stress and response. Therefore, mitochondrial function and signaling are considered significant modulators of carcinogenesis and cancer therapies. In addition, they also lie at the center of immunity. In fact, mitochondria can act as a platform for innate immune signaling activation via the mitochondrial antiviral–signaling protein (MAVS) on its outer membrane. At the same time, since mitochondria are the major source of reactive oxygen species (ROS) production, mitochondrial DNA (mtDNA) is constantly under oxidative stress that, if not overcome, generates a progressive accumulation of deleterious mutations. Ultimately, this leads to mitochondrial dysfunctions and release of mtDNA in the cytosol, where it acts as a danger-associated molecular pattern (DAMP) capable of activating major innate immune signaling pathways, such as TLR9 and cGAS/STING. Mitochondrial metabolic dysfunctions associated with mtDNA mutations have been observed in various cancers and are strictly correlated with poor prognosis in patients.

This Special Issue will review several aspects of next-generation cancer therapy and mitochondrial function pathway during cancer development and progression. A deeper understanding of mitochondrial metabolic dysfunctions and signaling will provide important insight into a fundamental facet of tumor cell biology and may also reveal novel pathways for therapeutic intervention.

Dr. Tasleem Arif
Dr. M. Dafne Cardamone
Dr. Vaibhav Jain
Guest Editors

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• mitochondria
• cancer cell
• metabolism
• signaling
• mtDNA
• ROS
• mitochondrial dysfunction
• metabolic pathways
• inflammation
• therapy targets