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MP31 brings therapeutic promise for micropeptides

N. Huang, F. Li, M. Zhang, H. Zhou, Z. Chen, X. Ma, L. Yang, X. Wu, J. Zhong, F. Xiao, X. Yang, K. Zhao, X. Li, X. Xia, Z. Liu, S. Gao, N. Zhang, An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism. Cell Metab. 33, 128-144.e9 (2021).

Nu Zhang and colleagues present a tour-de-force effort to discovery, characterize and potentially therapeuterize a novel micropeptide MP31 against glioblastoma. MP31 is encoded by a uORF in PTEN and inhibits lactate dehydrogenase activity by competing with NAD+ at LDHA/B. MP31 thereby puts the brakes on lactate metabolism and holds promise for combating lactate-dependent tumors such as GBM. A true masterpiece of SEP/sORF discovery!

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