Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease

The perception of lysosomes and mitochondria as entirely separate and independent entities, whose sole functions are to degrade material and produce ATP respectively, has been challenged in recent years ,as more complex roles for both organelles as well as an unanticipated level of interdependence, are discovered. Coupled lysosome and mitochondrial function and dysfunction involves complex crosstalk between the two organelles, our understanding of which has been transformed by major advances in the field of membrane contact sites biology. We now know that membrane contact sites between lysosomes and mitochondria play central roles in inter-organelle communication. The importance of mitochondria-lysosome contacts (MLCs) in cellular homeostasis, evinced by the growing number of diseases that have been associated with their dysregulation, is starting to be appreciated. How MLCs are regulated and their coordination with other pathways of lysosome-mitochondria crosstalk is achieved is the subject of ongoing scrutiny and here we explore the current understanding of the complex crosstalk governing coupled function of the two organelles and the impact of coupled dysfunction in cellular stress and disease.