Rutgers Cancer Institute of New Jersey, New Brunswick, United States.
Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, United States.
Elife. 2020 Nov 25;9:e62377. doi: 10.7554/eLife.62377.
Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11) is the major energy sensor for cells to respond to metabolic stress. Autophagy degrades and recycles proteins, macromolecules, and organelles for cells to survive starvation. To assess the role and cross-talk between autophagy and Lkb1 in normal tissue homeostasis, we generated genetically engineered mouse models where we can conditionally delete and autophagy essential gene, throughout the adult mice. We found that Lkb1 was essential for the survival of adult mice, and autophagy activation could temporarily compensate for the acute loss of Lkb1 and extend mouse life span. We further found that acute deletion of Lkb1 in adult mice led to impaired intestinal barrier function, hypoglycemia, and abnormal serum metabolism, which was partly rescued by the Lkb1 loss-induced autophagy upregulation via inhibiting p53 induction. Taken together, we demonstrated that autophagy and Lkb1 work synergistically to maintain adult mouse homeostasis and survival.
肝激酶 B1（LKB1），也被称为丝氨酸/苏氨酸激酶 11（STK11），是细胞对代谢应激做出反应的主要能量传感器。自噬可降解和回收蛋白质、大分子和细胞器，使细胞在饥饿时得以存活。为了评估自噬和 Lkb1 在正常组织稳态中的作用和相互作用，我们构建了遗传工程小鼠模型，可在成年小鼠中条件性删除 和自噬必需基因 。我们发现 Lkb1 对成年小鼠的存活至关重要，而自噬的激活可以暂时补偿 Lkb1 的急性缺失并延长小鼠的寿命。我们进一步发现，成年小鼠中 Lkb1 的急性缺失导致肠道屏障功能受损、低血糖和异常的血清代谢，通过抑制 p53 诱导，Lkb1 缺失诱导的自噬上调部分挽救了这些表型。总之，我们证明了自噬和 LKB1 协同作用以维持成年小鼠的体内平衡和存活。
