Mitochondrial rewiring through mitophagy and mitochondrial biogenesis in cancer stem cells: A potential target for anti-CSC cancer therapy

Cancer stem cells (CSCs) are distinct subpopulations of cancer cells with stem cell-like abilities and are more resilient to chemotherapy, causing tumor relapse. Mitophagy, a selective form of autophagy, removes damaged unwanted mitochondria from cells through a lysosome-based degradation pathway to...

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Bibliographic Details
Published in:Cancer letters 2021-02, Vol.498, p.217-228
Main Authors: Praharaj, Prakash Priyadarshi, Panigrahi, Debasna Pritimanjari, Bhol, Chandra Sekhar, Patra, Srimanta, Mishra, Soumya Ranjan, Mahapatra, Kewal Kumar, Behera, Bishnu Prasad, Singh, Amruta, Patil, Shankargouda, Bhutia, Sujit Kumar
Format: Article
Language:English
Subjects:
Anti-CSC cancer therapy
Apoptosis
Autophagy
Bioenergetics
Biosynthesis
Breast cancer
Cancer
Cancer stem cell
Cancer therapies
Cell Differentiation - physiology
Chemotherapy
Drug resistance
Drug Resistance, Neoplasm - physiology
Efficiency
Gene regulation
Homeostasis
Humans
Hypoxia
Kinases
Leukemia
Metabolic reprograming
Metabolism
Metastasis
Mitochondria
Mitochondria - pathology
Mitochondria - physiology
Mitochondrial biogenesis
Mitophagy
Mitophagy - physiology
Neoplastic Stem Cells - pathology
Organelle Biogenesis
Phagocytosis
Phenotypes
Phosphorylation
Proteins
Stem cells
Transcription factors
Tumorigenesis
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Summary:Cancer stem cells (CSCs) are distinct subpopulations of cancer cells with stem cell-like abilities and are more resilient to chemotherapy, causing tumor relapse. Mitophagy, a selective form of autophagy, removes damaged unwanted mitochondria from cells through a lysosome-based degradation pathway to maintain cellular homeostasis. CSCs use mitophagy as a chief survival response mechanism for their growth, propagation, and tumorigenic ability. Mitochondrial biogenesis is a crucial cellular event replacing damaged mitochondria through the coordinated regulation of several transcription factors to achieve the bioenergetic demands of the cell. Because of the high mitochondrial content in CSCs, mitochondrial biogenesis is an interesting target to address the resistance mechanisms of anti-CSC therapy. However, to what extent both mitophagy and mitochondrial biogenesis are vital in promoting stemness, metabolic reprogramming, and drug resistance in CSCs has yet to be established. Therefore, in this review, we focus on understanding the interesting aspects of mitochondrial rewiring that involve mitophagy and mitochondrial biogenesis in CSCs. We also discuss their coordinated regulation in the elimination of CSCs, with respect to stemness and differentiation of the CSC phenotype, and the different aspects of tumorigenesis such as cancer initiation, progression, resistance, and tumor relapse. Finally, we address several other unanswered questions relating to targeted anti-CSC cancer therapy, which improves patient survival. •Cancer stem cells (CSCs) exploit mitophagy for their survival and stemness maintenance.•CSCs trigger mitochondrial biogenesis for their proper functioning and phenotypic alteration.•CSCs rely on mitophagy for their metabolic reprogramming to acclimatize to stressful environments.•Targeted inhibition of mitophagy and mitochondrial biogenesis effectively eliminates CSCs.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2020.10.036