Figure 1.

Model for the physical and functional interaction between mitochondria and lysosomes. Boxed areas represent outstanding questions: (1) The physical interaction between mitochondria and lysosomes occurs through vCLAMP in yeast but the identity of the proteins mediating this interaction in mammalian cells remain to be determined. (2) Lipid and amino acid metabolism are controlled by both lysosomes and mitochondria. However, how the interaction between the two organelles affects metabolism is still unknown. Possible mechanisms include lipid and amino acid transfer, as well as exchange of ions that regulate mitochondrial function. (3) Ca²⁺ is a key signaling molecule regulated by both lysosomes and mitochondria, in addition to the ER. Ca²⁺ activates several cellular processes including Calcineurin-dependent activation of TFEB and mitochondrial metabolism. As mitochondrial ROS stimulates lysosomal Ca²⁺ release, the role of Ca²⁺ in controlling lysosome-mitochondria cross-talk needs to be addressed. AA, amino acids; ETC, Electron transport chain; ER, Endoplasmic reticulum.