Regulation and Functions of Autophagy During Animal Development

Abstract

Autophagy is used to degrade cytoplasmic materials, and is critical to maintain cell and organismal health in diverse animals. Here we discuss the regulation, utilization and impact of autophagy on development, including roles in oogenesis, spermatogenesis and embryogenesis in animals. We also describe how autophagy influences postembryonic development in the context of neuronal and cardiac development, wound healing, and tissue regeneration. We describe recent studies of selective autophagy during development, including mitochondria-selective autophagy and endoplasmic reticulum (ER)-selective autophagy. Studies of developing model systems have also been used to discover novel regulators of autophagy, and we explain how studies of autophagy in these physiologically relevant systems are advancing our understanding of this important catabolic process.

Keywords: Autophagy; Development; Embryogenesis; Genetics; Oogenesis; Regeneration; Spermatogenesis.

Figure 1.. Different types of autophagy are used to deliver cytoplasmic materials to lysosomes.

Macroautophagy degrades cytosolic cargo components by delivery to lysosomes. Cytoplasmic cargoes are first associated with phagophore growth, autophagosome maturation, and subsequent trafficking and fusion with the lysosome. Chaperone-mediated autophagy (CMA) utilizes recognition of a KFERQ pentapeptide sequence along with Hsp70-mediated trafficking to the lysosome surface. Microautophagy involves direct sequestration of cytoplasmic material into lysosome.

Figure 2.. The role of autophagy in spermatogenesis.

Autophagy mutants exhibit multiple defects in sperm development, including defective clearance of paternal mitochondria, defects in sperm head morphogenesis and acrosome biogenesis, and defects in sperm motility and flagellar development.

Figure 3.. Selective autophagy of ER and mitochondria share common components.

PINK1 regulates both ER-phagy and mitophagy. Keap1 and Parkin act as rheostats for selective quality control, with Keap1 regulating ER-phagy and Parkin regulating mitophagy.

Figure 4.. Liquid-Liquid phase transition-based autophagy in C. elegans germline development.

P-granules are degraded in an autophagy-dependent manner. SEPA-1 is an adaptor for LGG-1-mediated autophagosome formation, where EPG-2 plays a role in the association of P-granules with early autophagic structures, EPG-3 plays roles in autophagosome formation, and EPG-5 regulates the late degradation of P-granules.