Related Experiment Video
Updated: Feb 27, 2026

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
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.
Abstract:
Mitochondrial dysfunction is common in cancer and the mitochondrial electron transport chain is often affected in carcinogenesis. To date, little is known about the expression of the ATP synthase subunits in clear cell renal cell carcinoma (ccRCC). The NextBio database was used to determine an expression profile of the ATP synthase subunits based on published microarray studies. We observed down-regulation of 23 out of 29 subunits of the ATP synthase. Differential expression was validated exemplarily for 12 genes (ATP5A1, ATP5B, ATPAF1, ATP5C1, ATP5D, ATP5O, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5I, ATP5S; screening cohort ccRCC n=18 and normal renal tissue n=10) using real-time PCR. Additional eight genes (ATP5A1, ATP5B, ATPAF1, ATP5F1, ATP5G1, ATP5G2, ATP5G3, ATP5S) were internally validated within an enlarged cohort (ccRCC n=74; normal renal tissue n=36). Furthermore, down-regulation of ATP5A1, ATPAF1, ATP5G1/G2/G3 was confirmed on the protein level using Western Blot and immunohistochemistry. We observed that altered expression of ATPAF1 and ATP5G1/G2/G3 was correlated with overall survival in patients with ccRCC. In conclusion, down-regulation of many ATP Synthase subunits occurs in ccRCC and is the basis for the reduced activity of the mitochondrial electron chain. Alteration of the expression of ATP5A1, ATPAF1, and ATP5G1/G2/G3 is characteristic for ccRCC and may be prognostic for ccRCC patients' outcome.
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.
Related Concept Videos
ATP Synthase: Mechanism
ATP Synthase: Structure
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...

