The CARD Research Project

Cellular homeostasis is driven by integrated activities of energy-supplying organelles, macromolecule-producing factories and recycling pathways. As in our modern society, power supply, production and effective waste disposal in the cell need to be in a constant equilibrium and respond to immediate internal and external demands. In cells, these operational networks are clustered into subcellular hubs (e.g. mitochondria for power supply; nucleus and ribosomes for macromolecules production; autophagy, lysosomes and proteasome for waste disposal and recycling), whose functions are regulated by complex signal transduction networks to ensure overall coordination.

Autophagy, a lysosomal process of self-eating, has recently emerged as a key player in the maintenance of cellular homeostasis. It ensures rapid removal of toxic materials as well as damaged and superfluous macromolecules and organelles, thereby providing means for waste disposal, and molecules for energy production and cellular renovation. Autophagy also participates in essential cell-fate decisions, e.g. stemness versus differentiation, and cell death versus survival. Autophagy research is gaining a great momentum worldwide, largely due to the recent identification of many autophagy- and lysosome-regulating genes, and their importance in numerous physiological and pathological conditions. The latter has made lysosomes and autophagy attractive targets for therapeutic intervention, especially in cancer and degenerative diseases. Molecular mechanisms regulating lysosomal integrity and autophagy are, however, only beginning to emerge, and essential questions concerning their crosstalk with other cellular processes as well as consequences of their deregulation have remained largely unanswered.