Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities
Abstract
:1. Introduction
2. Mitochondrial Alterations in Prostate Cancer
2.1. Mitochondrial Genome Variations
2.1.1. Copy Number Variation
2.1.2. Mutations
Mutation in Mitochondrial-Encoded Genes
Mutation in Nuclear-Encoded Mitochondrial Genes
2.2. Alteration of Mitochondrial Respiratory Complexes
2.3. Alteration of Mitochondrial Regulatory Factors
2.3.1. Mitochondrial ROS
2.3.2. Antioxidants
2.3.3. PGC1α
2.3.4. Androgen Receptor Signaling
2.3.5. Heat-Shock Proteins
3. Impact of Mitochondrial Alterations on Prostate Tumor Cell Phenotypes
3.1. Role in Prostate Tumor Cell Growth, Aggressiveness, and Epithelial-to-Mesenchymal Transition
3.2. Role in Therapy Resistance
3.3. Role in Evasion from Apoptosis
4. Mitochondrial Alterations in Stromal Remodeling
4.1. Mitochondrial Damage-Associated Molecular Patterns
4.2. Oncometabolites
5. Mitochondria Alteration in Prostate Cancer Racial Disparity
6. Translational Potential of Mitochondrial Alterations in Prostate Cancer
6.1. Mitochondrial Alterations as Prognostic Markers
6.2. Therapeutic Targeting of Mitochondrial Function
6.2.1. Targeting Prostate Cancer Metabolism
6.2.2. Targeting Mitochondrial Dynamics
6.2.3. Targeting Translocases and Solute Transporters of Mitochondria
7. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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S.N. | Gene/Variant | Function | Type of Cancer | Racial Disparity | Reference |
---|---|---|---|---|---|
1 | ERR1 and PGC1α | Mitochondrial biogenesis | Pan cancer | Strong enrichment of ERR1-PGC1α transcriptional program in AA tumors than EA | [126] |
2 | Cytochrome c oxidase subunit I (COI) | Oxidative phosphorylation, Mitochondrial supercomplex assembly | Prostate cancer | COI missense mutations more common in African American compare to others | [32,137] |
3 | POLG | Mitochondrial DNA replication | Prostate Cancer | CAG repeats variants in POLG associated with increased risk of breast cancer in African American Women | [138] |
4 | ND3 (G10398A) | Alters the structure of Complex I | Prostate cancer and Breast Cancer | Increased risk of breast cancer in African American women with G10398A allele | [139,140] |
5 | Haplogroup U (A11467G, A12308G, G12372A) | ----- | Prostate Cancer | Mitochondrial haplogroup U is associated with increased risk of prostate cancer in white North American individuals | [141] |
6 | HSP60 and HSP90 | Act as chaperones and support cancer cell survival | Prostate cancer | Compare to CA cells, lower expression of HSP60 and HSP90 in AA cells is associated with mitochondrial dysfunction, and chemoresistance | [142] |
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Vikramdeo, K.S.; Sharma, A.; Anand, S.; Sudan, S.K.; Singh, S.; Singh, A.P.; Dasgupta, S. Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities. Int. J. Mol. Sci. 2023, 24, 4482. https://doi.org/10.3390/ijms24054482
Vikramdeo KS, Sharma A, Anand S, Sudan SK, Singh S, Singh AP, Dasgupta S. Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities. International Journal of Molecular Sciences. 2023; 24(5):4482. https://doi.org/10.3390/ijms24054482
Chicago/Turabian StyleVikramdeo, Kunwar Somesh, Amod Sharma, Shashi Anand, Sarabjeet Kour Sudan, Seema Singh, Ajay Pratap Singh, and Santanu Dasgupta. 2023. "Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities" International Journal of Molecular Sciences 24, no. 5: 4482. https://doi.org/10.3390/ijms24054482