MCOLN3/TRPML3 bridges the regulation of autophagosome biogenesis by PtdIns3P and the calcium channel

In recent years, an increasing number of studies have started to investigate the roles of ions and ion channels in macroautophagy/autophagy. One finding is that calcium regulates multiple stages of autophagy with lysosomal calcium release being important for autophagosome and lysosome fusion. MCOLN3/TRPML3, as a calcium-permeable channel that is located on both lysosomes and autophagosomes, has been suggested as an autophagy regulator and a candidate to provide the calcium for autophagic fusion, but how this channel is activated remains unclear. In a recent article, Kim et al. demonstrate that MCOLN3 is a PtdIns3P downstream effector, and the activation of its channel function is critical for autophagosome biogenesis.