乳酸是由LDH（乳酸脱氢酶）将丙酮酸转化而来的糖酵解产物，在生理和病理过程中发挥着重要作用。然而，乳酸是否调节自噬仍然未知。我们最近报道，LDHA在营养剥夺条件下被ULK1（unc-51 like kinase 1）磷酸化于丝氨酸196位点，促进乳酸产生。然后，乳酸通过酰转移酶KAT5/TIP60介导PIK3C3/VPS34在赖氨酸356位点和赖氨酸781位点的乳酸化。PIK3C3/VPS34的乳酸化增强了其与BECN1（自噬相关的beclin 1）、ATG14和UVRAG的结合，提高了PIK3C3/VPS34的脂质激酶活性，促进了宏噬/自噬作用和内溶酶体降解途径。PIK3C3/VPS34的过度乳酸化诱导自噬，在骨骼肌稳态和癌症进展中扮演着重要角色。总之，本研究描述了一种自噬调节机制以及两个高度保守的生命过程之间的整合：糖酵解和自噬。

Lactate is a glycolysis product that is produced from pyruvate by LDH (lactate dehydrogenase) and plays an important role in physiological and pathological processes. However, whether lactate regulates autophagy is still unknown. We recently reported that LDHA is phosphorylated at serine 196 by ULK1 (unc-51 like kinase 1) under nutrient-deprivation conditions, promoting lactate production. Then, lactate mediates PIK3C3/VPS34 lactylation at lysine 356 and lysine 781 via acyltransferase KAT5/TIP60. PIK3C3/VPS34 lactylation enhances the association of PIK3C3/VPS34 with BECN1 (beclin 1, autophagy related), ATG14 and UVRAG, increases PIK3C3/VPS34 lipid kinase activity, promotes macroautophagy/autophagy and facilitates the endolysosomal degradation pathway. PIK3C3/VPS34 hyperlactylation induces autophagy and plays an essential role in skeletal muscle homeostasis and cancer progression. Overall, this study describes an autophagy regulation mechanism and the integration of two highly conserved life processes: glycolysis and autophagy.