Lysosomal calcium is emerging as a modulator of autophagy and lysosomal compartment, an obligatory partner to complete the autophagic pathway. A variety of specific signals such as nutrient deprivation or oxidative stress can trigger lysosomal calcium-mediated nuclear translocation of the transcription factor EB (TFEB), a master regulator of global lysosomal function. Also, lysosomal calcium can promote the formation of autophagosome vesicles (AVs) by a mechanism that requires the production of the phosphoinositide PI3P by the VPS34 autophagic complex and the activation of the energy-sensing kinase AMPK. Additionally, lysosomal calcium plays a role in membrane fusion and fission events involved in cellular processes such as endocytic maturation, autophagosome-lysosome fusion, lysosomal exocytosis, and lysosomal reformation upon autophagy completion. Lysosomal calcium-dependent functions are defective in cellular and animal models of the non-selective cation channel TRPML1, whose mutations in humans cause the neurodegenerative lysosomal storage disease mucolipidosis type IV (MLIV). Lysosomal calcium is not only acting as a positive regulator of autophagy, but it is also responsible for turning-off this process through the reactivation of the mTOR kinase during prolonged starvation. More recently, it has been described the role of lysosomal calcium on an elegant sequence of intracellular signaling events such as membrane repair, lysophagy, and lysosomal biogenesis upon the induction of different grades of lysosomal membrane damage. Here, we will discuss these novel findings that re-define the importance of the lysosome and lysosomal calcium signaling at regulating cellular metabolism.

溶酶体钙正在成为自噬和溶酶体区室的调节剂，是完成自噬途径的必要伙伴。各种特定信号，如营养剥夺或氧化应激，可触发溶酶体钙介导的转录因子 EB (TFEB) 核易位，TFEB 是全球溶酶体功能的主要调节因子。此外，溶酶体钙可以通过需要 VPS34 自噬复合物产生磷酸肌醇 PI3P 和激活能量感应激酶 AMPK 的机制促进自噬体囊泡 (AV) 的形成。此外，溶酶体钙在涉及细胞过程的膜融合和裂变事件中发挥作用，例如内吞成熟、自噬体-溶酶体融合、溶酶体胞吐作用、和自噬完成后的溶酶体重组。溶酶体钙依赖性功能在非选择性阳离子通道 TRPML1 的细胞和动物模型中存在缺陷，其在人类中的突变导致神经退行性溶酶体贮积症 IV 型粘液脂沉积症 (MLIV)。溶酶体钙不仅充当自噬的正调节剂，而且还负责通过在长期饥饿期间重新激活 mTOR 激酶来关闭这一过程。最近，已经描述了溶酶体钙在诱导不同级别的溶酶体膜损伤时对细胞内信号事件的优雅序列的作用，例如膜修复、溶血和溶酶体生物发生。这里，