Mitochondrial dysfunctions in bladder cancer: Exploring their role as disease markers and potential therapeutic targets

- Germline mtDNA mutations hold promise to identify men at risk of developing BC.
- MtDNA mutations and copy number provide encouraging results in BC early detection.
- Lon proteaseand TFAM may have prognostic value in BC.
- Lon protease, Mfn-2 and TFAM may represent novel potential therapeutic targets.

Bladder cancer (BC) is a major cause of mortality worldwide as it currently lacks fully reliable markers of disease outcome and effective molecular targets for therapy. Mitochondria play a key role in cell metabolism but the role of mitochondrial dysfunctions in BC has been scarcely investigated. In this review, we explored current evidence for the potential role of mitochondrial DNA (mtDNA) alterations (point mutations and copy number) as disease markers in BC. Some germline mtDNA mutations detectable in blood could represent a non-invasive tool to predict the risk of developing BC. MtDNA copy number and tumor specific mtDNA mutations and RNAs showed encouraging results as novel molecular markers for early detection of BC in body fluids. Moreover, mitochondrial proteins Lon protease, Mitofusin-2, and TFAM may have prognostic/predictive value and may represent potential therapeutic targets. A deeper understanding of mitochondrial dysfunctions in BC could therefore provide novel opportunities for targeted therapeutic strategies.