p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation

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Shaoping Tian1, Rui Wang1, Yiting Wang2

  • 1Department of Microbiology, School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China.

International Journal of Biological Sciences
|January 3, 2024
PubMed

Insights

Reduced p32 protein in kidney cancer (ccRCC) impairs mitochondrial function by affecting the pyruvate dehydrogenase complex (PDHc) and TCA cycle. Restoring p32 enhances oxidative phosphorylation and may offer new therapeutic targets.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • p32 (C1QBP) is a mitochondrial protein crucial for respiration.
  • Previous work established p32's interaction with DLAT within mitochondria.
  • Altered mitochondrial metabolism is a hallmark of clear cell renal cell carcinoma (ccRCC).

Purpose of the Study:

  • To investigate the role of p32 in ccRCC progression and metastasis.
  • To elucidate the mechanism by which p32 regulates mitochondrial metabolism in ccRCC.
  • To identify novel molecular targets for ccRCC therapy.

Main Methods:

  • Analysis of p32 expression in ccRCC tissues and animal models.
  • Studies on the interaction between p32, DLAT, and copper.
  • Assessment of oxidative phosphorylation, pyruvate dehydrogenase complex (PDHc) activity, and TCA cycle flux.

Main Results:

  • p32 expression is significantly reduced in ccRCC, correlating with suppressed tumor progression and metastasis.
  • Increased p32 enhances oxidative phosphorylation via DLAT interaction, activating PDHc.
  • p32 binds copper, promoting lipo-DLAT oligomerization and regulating ccRCC cell glycometabolism and TCA cycle.

Conclusions:

  • The p32/DLAT/copper complex plays a critical role in ccRCC metabolic reprogramming.
  • Reduced p32 impairs mitochondrial function by suppressing PDHc activity and the TCA cycle.
  • This study reveals novel insights into ccRCC-associated abnormal mitochondrial metabolism, highlighting p32 as a potential therapeutic target.
Keywords:
Clear cell renal cell carcinomaCopperDLATglycometabolismp32tricarboxylic acid cycle

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