The gap between prostate cancer disparities among American men is narrowing, which is mostly due to increased screening of African American (AA) men. However, the biological reasons for prostate cancer disparities among American men still remain undefined. Mitochondrion, an organelle within cells, regulates both cell survival and cell death mechanisms. These cellular signaling pathways require various proteins localized to mitochondria, which are encoded by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Interestingly, prostate tissues from AA men harbor reduced mtDNA content compared to Caucasian American (CA) men. Therefore, changes in mitochondrial genes may have detrimental consequences in terms of cellular signaling regulated by mitochondria in AA men. This review describes the plausible underlying mechanism of mtDNA depletion and its impact in driving resistance to therapy leading to faster progression and poor prognosis in African American men with prostate cancer. Since defective cellular signaling is critical for prostate cancer cell survival, restoring mitochondrial function may provide strategies to alleviate prostate cancer disparities among American men.
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