Systematic Analysis of the Expression of the Mitochondrial ATP Synthase (Complex V) Subunits in Clear Cell Renal Cell

Maria Brüggemann1, Arabella Gromes1, Mirjam Poss1

  • 1University Hospital Bonn, Department of Urology, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.

Insights

Mitochondrial dysfunction is common in clear cell renal cell carcinoma (ccRCC). Many ATP synthase subunits are down-regulated, impacting the electron transport chain and patient survival.

Area of Science:

  • Oncology
  • Mitochondrial Biology
  • Biochemistry

Background:

  • Mitochondrial dysfunction is prevalent in cancer, particularly affecting the electron transport chain.
  • The expression of ATP synthase subunits in clear cell renal cell carcinoma (ccRCC) is largely uncharacterized.

Purpose of the Study:

  • To investigate the expression profile of ATP synthase subunits in ccRCC.
  • To determine if altered ATP synthase subunit expression correlates with patient prognosis.

Main Methods:

  • Utilized the NextBio database for initial expression profiling of ATP synthase subunits.
  • Validated gene expression using real-time PCR in ccRCC and normal renal tissue cohorts.
  • Confirmed protein-level changes via Western Blot and immunohistochemistry.

Main Results:

  • Down-regulation of 23 out of 29 ATP synthase subunits was observed in ccRCC.
  • Differential expression was validated for multiple subunits, including ATP5A1, ATPAF1, and ATP5G1/G2/G3.
  • Altered expression of ATPAF1 and ATP5G1/G2/G3 correlated with overall survival in ccRCC patients.

Conclusions:

  • Down-regulation of ATP synthase subunits is a characteristic feature of ccRCC, contributing to reduced mitochondrial electron chain activity.
  • Altered expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 serves as a potential prognostic marker for ccRCC patient outcomes.

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