Ca2+ efflux from the lysosome carries the signals needed for precise delivery of hydrolases and cargo, as well as timely removal of digested catabolites. Impaired homeostasis of lysosomal Ca2+ causes lysosomal dysfunction and lysosomal storage diseases (LSDs). By directly patch-clamping lysosomal membranes, we have recently demonstrated that Mucolipin Transient Receptor Potential protein 1 (TRPML1 or ML1) is the principle Ca2+ channel in late endosomes and lysosomes. Human mutations in TRPML1 result in type IV Mucolipidosis (ML-IV) neurodegenerative LSD, and at the cellular level, lysosomal trafficking defects and lysosome storage. Upon nutrient starvation, autophagy digests unwanted cellular components to generate catabolites that are required for housekeeping biosynthesis processes. A complete execution of autophagy demands an enhancement in lysosome function and biogenesis to match the increase in autophagosome formation. We report that lysosomal TRPML1 channels play a central role in this quality-control process. By using Ca2+ imaging and whole-lysosome patch clamping, lysosomal Ca2+ release and ML1 currents were detected within hours of nutrient starvation and were potently up-regulated. In contrast, lysosomal Na+-selective currents were not upregulated. Inhibition of mammalian target of rapamycin (mTOR) or activation of transcription factor EB (TFEB) mimicked a starvation effect in fed cells. The starvation effect also included an increase in lysosomal proteostasis and enhanced clearance of lysosomal storage. However, this effect was not observed when TRPML1 was pharmacologically inhibited or genetically deleted. Hence,lysosomal adaptation to environmental cues such as nutrient levels requires mTOR/TFEB-dependent, lysosome-to-nucleus regulation of lysosomal TRPML1 channels and Ca2+ signaling.