Eat, Heal, Repeat: How zebrafish master regeneration

For eukaryotic organisms the maintenance and regulation of cellular homeostasis is essential. This process requires continuous elimination of cellular debris, including misfolded, oxidized, and aggregated proteins, and damaged/obsolete organelle. It also requires the remodelling of the cytoplasm compartments, and the provision of nutrients to support basic cellular functions. One of the central molecular mechanisms that maintain this precarious homeostasis is the recycling program of the cell: autophagy. Dysregulation of autophagy has a relationship with several diseases, including neurodegeneration, metabolic diseases, age-related disorders, heart dysfunction, cancer, and inflammatory diseases. The regeneration of some tissues and organs in humans is limited, which hinders our capacity to recover from diseases. Regenerative ability varies from species, organs, tissues, and development stages. Whereas mammals have a more limited regenerative capacity, restricted to few tissues or organs, such as skin or liver, other vertebrates, such as axolotls, salamanders, goldfish and zebrafish, possess a higher regenerative capacity. Zebrafish display exceptional regenerative abilities. Both embryo and adult zebrafish can regenerate organs like the fin, heart, liver, kidney, muscle, spinal cord, retina and optic nerves, and several brain regions. In recent years, several works remark the crucial role of autophagy in the repair of damaged tissues and the replacement of impaired organs or body parts after injury. Investigating the cellular function of autophagy in regenerative processes will allow us to develop new therapeutic strategies for human disorders. In this chapter, we discuss the current evidence supporting the important role of autophagy in mediating regenerative processes, emphasizing the relevance of zebrafish as a prominent vertebrate model to study autophagy.