Wang (Fei) Lab

Autophagy is a lysosomal degradation pathway. Numerous human diseases, such as cancer, and infectious and developmental diseases have been linked to aberrant autophagy. Besides its disease relevance, autophagy is a unique system for investigating the basic principles of organellar biogenesis because, unlike many organelles that are rich in membrane and protein components (endoplasmic reticulum, mitochondria, etc), autophagosomes are relatively simple. Autophagosomal biogenesis responds to a variety of internal and external signals, making fine genetic or chemical manipulation possible for understanding molecular mechanisms and defining new targets for disease treatment. Canonically, nascent autophagosomes fuse with lysosomes to deliver their cargos for degradation. However, under certain circumstances, autophagosomes appear to also have degradation-independent functions, for example, protein secretion. We propose that the canonical and non-canonical roles of autophagosomes co-operate to guide cells through critical stages of development, such as meiosis, when the cell is programmed to undergo drastic cellular content degradation and structural remodeling. We demonstrated that, while autophagy is dispensable for mitosis, it is essential for meiosis at multiple stages (Dev Cell, 2020). We discovered that the conserved phosphatase Cdc14 directly activates autophagy during meiotic divisions, establishing the first mechanistic, meiosis-specific “on-switch” for autophagy (J. Cell Biol., 2022), and that the meiosis-specific RNA-binding protein Rim4—an essential repressor of post-transcriptional meiotic gene expression—is both a selective autophagy substrate and the master regulator of meiotic stress granules (Cell Reports, 2023a,b; Nat. Commun., 2025). These findings reveal how the evolutionarily conserved enzymes PKA, Cdc14, and 14-3-3 proteins coordinate Rim4’s phosphorylation state and spatiotemporal dynamics to couple translational repression, autophagic degradation, and stress adaptation with meiotic progression. Our ongoing studies will keep shedding light directly on autophagy functions in eukaryotic gametogenesis, the production of sperm (spermatogenesis) and oocytes (oogenesis).