Lactylation, the covalent modification of lysine with lactate, is a recently identified post-translational modification, and the full extent of its substrates as well as physiological role and effects are only beginning to be revealed. Wei Liu and colleagues report the lactylation of TFEB, the master regulator of lysosome biogenesis and autophagy, which results in its stabilization and promotes autophagy.

By addressing the mechanism underlying TFEB stabilization, the authors show that lactylation at K91, the only lactylation site in TFEB, prevents it from interacting with the E3 ubiquitin ligase WWP2, inhibiting its ubiquitination and subsequent proteasomal degradation. These findings are also relevant for cancer; by using a specific anti-lactyl-K91 antibody they generated, the authors detected increased TFEB-lactylation levels in human primary pancreatic ductal adenocarcinoma samples, pointing to a possible molecular mechanism for the known increase in autophagy in cancer cells.

乳酰化是赖氨酸与乳酸的共价修饰，是最近发现的翻译后修饰，其底物的全部范围以及生理作用和影响才刚刚开始显现。Wei Liu 及其同事报道了 TFEB 的乳酸化，TFEB 是溶酶体生物发生和自噬的主要调节因子，这导致其稳定并促进自噬。

通过解决 TFEB 稳定的潜在机制，作者表明 T91 的乳酰化是 TFEB 中唯一的乳酸化位点，可防止其与 E3 泛素连接酶 WWP2 相互作用，从而抑制其泛素化和随后的蛋白酶体降解。这些发现也与癌症有关;通过使用他们产生的特异性抗乳酰 K91 抗体，作者检测到人原发性胰腺导管腺癌样本中 TFEB-乳酸化水平增加，指出了癌细胞中已知自噬增加的可能分子机制。