Diving into the cellular puzzle: Exploring the connection between mitochondrial DNA depletion and prostate cancer development

Year 2024, Volume: 41 Issue: 3, 663 - 669, 30.09.2024

Dilbeste Demir Yeşilyurt , Sercan Ergün , Neslihan Hekim , Sezgin Güneş

Abstract

Mitochondria, essential components of eukaryotic cells, play a central role in generating cellular energy, regulating metabolism, and facilitating cellular interactions. A distinguishing characteristic of mitochondria is their unique circular double-stranded DNA, known as mitochondrial DNA (mtDNA), essential for energy synthesis and overall mitochondrial function. MtDNA depletion is a notable decrease in mtDNA levels and is affected by a combination of genetic and environmental elements. Genetic contributors include inherited mutations, nuclear DNA changes that impact mitochondrial activity, and mutations within the D-loop region of mtDNA. Environmental factors encompass exposure to specific medications, oxidative stress, and insufficient nutrient consumption. Prostate cancer, a primary contributor to male cancer fatalities, has been associated with anomalies in mtDNA structure and function. The involvement of mitochondria in prostate cancer is intricate, influencing energy metabolism, the stability of the genome, and the emergence of aggressive, androgen-independent cancer variants. Notably, mtDNA depletion is implicated in the shift from androgen-sensitive to androgen-resistant prostate cancer, emphasizing its crucial role in disease advancement. Additionally, mtDNA depletion correlates with the development of a cancer stem cell-like phenotype, marked by increased tumor aggressiveness and heightened resistance to therapeutic agents. Research indicates that changes in mtDNA quantity are linked to the progression and prognosis of prostate cancer. Elevated levels of POLRMT, a nuclear enzyme essential for mtDNA synthesis, have been associated with prostate cancer proliferation, while diminished mtDNA levels are linked to increased invasiveness and a shift towards a mesenchymal cell state. In summary, grasping the intricate relationship between mtDNA depletion and prostate cancer is essential for formulating targeted treatment approaches and enhancing patient outcomes. This review article emphasizes the critical role of mtDNA in the advancement of prostate cancer and underscores its potential as a therapeutic focal point in addressing this widespread cancer.

Keywords

Prostate cancer, androgen dependence, cancer stem cell, mitochondrial DNA depletion, mitochondrial DNA copy number

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