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Int J Biol Sci 2024; 20(2):516-536. doi:10.7150/ijbs.84399 This issue Cite

Research Paper

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

Shaoping Tian1*, Rui Wang1*, Yiting Wang3*, Ruibing Chen4, Tianyu Lin1, Xuesong Xiao2, Xinyu Liu1, Justin Eze Ideozu5, Hua Geng6, Yong Wang2✉, Dan Yue1✉

1. Department of Microbiology, School of Medical Laboratory, Tianjin Medical University, Tianjin 300203, China.
2. Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
3. Department of Clinical Laboratory, Tianjin Children's Hospital/Tianjin University Children's Hospital, Tianjin 300134, China.
4. School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.
5. Genomic Medicine, Genomic Research Center, AbbVie, North Chicago, IL 60064, USA.
6. Department of Pediatrics, University of Illinois at Chicago, Chicago, IL, USA.
*Shaoping Tian, Rui Wang and Yiting Wang contributed equally to this work.

✉ Corresponding authors: Yong Wang: wyedu.cn, Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, 23 Pingjiang Rd, Hexi District, Tianjin 300211, China. Dan Yue: yuedanedu.cn, Department of More

Citation:
Tian S, Wang R, Wang Y, Chen R, Lin T, Xiao X, Liu X, Ideozu JE, Geng H, Wang Y, Yue D. p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. Int J Biol Sci 2024; 20(2):516-536. doi:10.7150/ijbs.84399. https://www.ijbs.com/v20p0516.htm
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Abstract

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A key player in mitochondrial respiration, p32, often referred to as C1QBP, is mostly found in the mitochondrial matrix. Previously, we showed that p32 interacts with DLAT in the mitochondria. Here, we found that p32 expression was reduced in ccRCC and suppressed progression and metastasis in ccRCC animal models. We observed that increasing p32 expression led to an increase in oxidative phosphorylation by interacting with DLAT, thus, regulating the activation of the pyruvate dehydrogenase complex (PDHc). Mechanistically, reduced p32 expression, in concert with DLAT, suppresses PDHc activity and the TCA cycle. Furthermore, our research discovered that p32 has a direct binding affinity for copper, facilitating the copper-induced oligomerization of lipo-DLAT specifically in ccRCC cells. This finding reveals an innovative function of the p32/DLAT/copper complex in regulating glycometabolism and the TCA cycle in ccRCC. Importantly, our research provides important new understandings of the underlying molecular processes causing the abnormal mitochondrial metabolism linked to this cancer.

Keywords: Clear cell renal cell carcinoma, p32, glycometabolism, DLAT, tricarboxylic acid cycle, Copper

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APA
Tian, S., Wang, R., Wang, Y., Chen, R., Lin, T., Xiao, X., Liu, X., Ideozu, J.E., Geng, H., Wang, Y., Yue, D. (2024). p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. International Journal of Biological Sciences, 20(2), 516-536. https://doi.org/10.7150/ijbs.84399.

ACS
Tian, S.; Wang, R.; Wang, Y.; Chen, R.; Lin, T.; Xiao, X.; Liu, X.; Ideozu, J.E.; Geng, H.; Wang, Y.; Yue, D. p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. Int. J. Biol. Sci. 2024, 20 (2), 516-536. DOI: 10.7150/ijbs.84399.

NLM
Tian S, Wang R, Wang Y, Chen R, Lin T, Xiao X, Liu X, Ideozu JE, Geng H, Wang Y, Yue D. p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. Int J Biol Sci 2024; 20(2):516-536. doi:10.7150/ijbs.84399. https://www.ijbs.com/v20p0516.htm

CSE
Tian S, Wang R, Wang Y, Chen R, Lin T, Xiao X, Liu X, Ideozu JE, Geng H, Wang Y, Yue D. 2024. p32 regulates glycometabolism and TCA cycle to inhibit ccRCC progression via copper-induced DLAT lipoylation oligomerization. Int J Biol Sci. 20(2):516-536.

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