The ovaries play essential roles in providing oocytes for fertilization and secreting sex hormones that regulate various organ functions. Autophagy has been implicated in the modulation of ovarian functions, yet its mechanisms of action are complex and context-dependent. Within the ovary, autophagy fulfills a dual function, serving as a critical mechanism in facilitating oocyte development, maintaining granulosa cell viability, regulating hormone synthesis, ovulation and luteal function. Conversely, dysregulation of autophagy can interact with other death signals, leading to cell death of ovarian cells, and has been linked to the development of diminished ovarian reserve (DOR), premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Emerging evidence suggests that pharmacological modulation of autophagy exerts significant therapeutic effects on POI and PCOS. Despite this association, numerous unresolved issues persist in this field of research. This paper provides a comprehensive overview of the context-dependent roles of autophagy in ovarian physiology and disorders, and proposes potential applications of autophagy-based interventions as therapeutic strategies for addressing ovarian dysfunctions.

Ahmad, M. H., Rizvi, M. A., Ali, M. & Mondal, A. C. Neurobiology of depression in Parkinson’s disease: insights into epidemiology, molecular mechanisms and treatment strategies. Ageing Res. Rev. 85, 101840 (2023). Ben-Shlomo, Y. et al. The epidemiology of Parkinson’s...

Tumor necrosis factor (TNF), type I interferons (IFNs), and autophagy are important biological processes, but their interactions in inflammation have not been explored. In this issue of Immunity, Prie...

The ovaries play essential roles in providing oocytes for fertilization and secreting sex hormones that regulate various organ functions. Autophagy has been implicated in the modulation of ovarian functions, yet its mechanisms of action are complex and context-dependent. Within the ovary, autophagy fulfills a dual function, serving as a critical mechanism in facilitating oocyte development, maintaining granulosa cell viability, regulating hormone synthesis, ovulation and luteal function. Conversely, dysregulation of autophagy can interact with other death signals, leading to cell death of ovarian cells, and has been linked to the development of diminished ovarian reserve (DOR), premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS). Emerging evidence suggests that pharmacological modulation of autophagy exerts significant therapeutic effects on POI and PCOS. Despite this association, numerous unresolved issues persist in this field of research. This paper provides a comprehensive overview of the context-dependent roles of autophagy in ovarian physiology and disorders, and proposes potential applications of autophagy-based interventions as therapeutic strategies for addressing ovarian dysfunctions.

Galectin-3 (Gal-3) is a carbohydrate-binding protein which plays crucial roles in inflammation, immune response, cell migration, autophagy, and signaling. At the ocular surface, Gal-3 is also known to crosslink transmembrane mucins across the epithelial cell glycocalyx, forming lattice structures important for barrier function. However, the biological role of Gal-3 in circulating tear fluid remains largely unexplored. Similarly, whether Gal-3 engages extracellular glycoproteins in tears to affect downstream biological processes has yet to be investigated. As increased Gal-3 levels in tears are known to correlate with ocular pathologies such as dry eye disease (DED), we sought to elucidate the Gal-3 interactome in tear fluid and uncover biological insights into the function of Gal-3 beyond adhesion to the epithelial cell surface. Here, we combined ELISA, lectin affinity enrichment, mass spectrometry (MS)-based glycoproteomics, and lectin blotting to uncover Gal-3 interactors and their associated glycoepitopes. Overall, we report nearly 100 proteins enriched from tear fluid across 3 different patients, identifying proteins involved in immune response, inflammation, and antimicrobial activity. Most notably, we report lacritin as a novel ligand for Gal-3 and demonstrate that specific glycoforms of lacritin bearing core 2 O-glycans preferentially engage with Gal-3. Lastly, we show that the Gal-3-lacritin axis is spliceoform-specific and dependent on lacritin multimerization. Taken together, this study elucidates new ligands for Gal-3 in tear film and reveals mRNA splicing and multimerization as new biochemical mechanisms that fine-tune Gal-3 binding events.

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Emerging evidence reveals that dysregulated autophagy, particularly the selective degradation of lipid droplets (lipophagy), is crucial to maintaining hepatic lipid balance, yet how its activity is re...

Autophagy maintains cellular homeostasis through lysosomal degradation of cytoplasmic components, yet how prolonged autophagy activation reshapes organelle architecture remains poorly understood. Here...