Mitochondrial SLC25A10 promotes prostate cancer progression by inhibiting ferritinophagy

Prostate cancer (PCa) is one of the most common malignancies in men worldwide and remains a major cause of cancer-related mortality. Despite advances in early diagnosis and treatment, a significant proportion of patients eventually progress to advanced or treatment-resistant disease, highlighting the urgent need for novel therapeutic targets and strategies. In this study, we systematically analyzed transcriptomic data from The Cancer Genome Atlas (TCGA) and performed Venn analysis to identify genes associated with PCa progression. Among the intersecting candidates, SLC25A10, a mitochondrial carrier protein, emerged as a potential key regulator of ferroptosis. Further expression analyses revealed that SLC25A10 is significantly upregulated in PCa tissues and correlates with poor prognosis. Functional gain- and loss-of-function experiments demonstrated that SLC25A10 promotes tumor cell proliferation, migration, and invasion, while exacerbating mitochondrial dysfunction and impairing autophagic flux. Mechanistically, mass spectrometry and co-immunoprecipitation (Co-IP) assays confirmed a direct interaction between SLC25A10 and P62, implicating this interaction in the suppression of autophagy and the promotion of ferroptotic vulnerability. Moreover, disruption of the SLC25A10/p62/KEAP1/Nrf2 signaling axis reactivated autophagy and inhibited PCa cell growth. Collectively, our findings uncover a novel oncogenic role of SLC25A10 in PCa and suggest that targeting the SLC25A10-mediated regulatory network may offer a promising therapeutic avenue for patients with advanced prostate cancer.