Ubiquitin-fold modifier 1 (UFM1) is a ubiquitin-like molecule (UBL) discovered almost two decades ago, but our knowledge about the cellular and molecular mechanisms of this novel protein post-translational modification is still very fragmentary. In this review, we first summarize the core enzymes and factors involved in the UFMylation cascade, which, similar to ubiquitin, is consecutively catalyzed by UFM1-activating enzyme 5 (UBA5), UFM1-conjugating enzyme 1 (UFC1) and UFM1-specific ligase 1 (UFL1). Inspired by the substantial implications of UFM1 machinery in the secretory pathway, we next concentrate on the puzzling role of UFMylation in maintaining ER protein homeostasis, intending to illustrate the underlying mechanisms and future perspectives. At last, given a robust ER network is a hallmark of healthy endocrine secretory cells, we emphasize the function of UFM1 modification in physiology and pathology in the context of endocrine glands pancreas and female ovaries, aiming to provide precise insight into other internal glands of the endocrine system.

Ufmylation is a recently identi ed small ubiquitin-like modi cation, whose biological function and relevant cellular targets are poorly understood. Here we present evidence of a neuroprotective role for Ufmylation involving Autophagy-related gene 9 (Atg9) in the aging brain of Drosophila. The Ufm1 system ensures the health of aged neurons via Atg9 by coordinating autophagy and mTORC1, and maintaining mitochondrial homeostasis and JNK (c-Jun N-terminal kinase) activity. Neuron-speci c expression of Atg9 suppresses the age-associated movement defect and lethality caused by loss of Ufmylation. Furthermore, Atg9 is identi ed as a conserved target of Ufm1 conjugation mediated by Ddrgk1, a critical regulator of Ufmylation. Mammalian Ddrgk1 was shown to be indispensable for the stability of endogenous Atg9A protein in mouse embryonic broblast (MEF) cells. Taken together, our ndings might have important implications for neurodegenerative diseases in mammals.

This study was conducted to systematically assess and compare the fluctuations in crude protein (CP), crude fat (CF) and mineral content of staged (larva to adult) Drosophila (fruit fly) to that of a market-purchased black soldier fly larvae (BSFL) product. Results suggested that the relative CP content by dry matter ranged from 40.11-53.73% during Drosophila development, significantly higher (P<0.001) than the 36.90% in BSFL. The relative CF was higher in BSFL (39.14%) compared to that of Drosophila (27.03-30.10%, P<0.001). Although both insects contained sufficient levels of minerals to meet the dietary requirements of most animals, Drosophila overall possessed a lower content of iron, sodium and calcium (P<0.001) with a higher gross energy than the BSFL (P<0.01). Comparative studies of amino acid (AA) and fatty acid (FA) profiles were further carried out among Drosophila larva (DL), pupa and BSFL for their economic effectiveness. The AA spectra of insect larvae generally were similar except that the DL was higher in certain AA such as lysine (P<0.01), which is an essential AA often critical for chicken growth. In contrast, the BSFL included more essential FA such as linoleic (C18:2, ω-6) and linolenic (C18:3, ω-3) acids (P<0.01). To follow up, a husbandry trial was performed by allotting 120, 1-day-old, weight-matched, Arbor Acres broilers at random into treatment groups consisting of a low-protein diet background that contained ~20% CP supplemented with 4% BSFL and 4% or 8% DL. The average daily growth (ADG) and average daily feed intake (ADFI) of broilers, compared to the control low-protein diet, were significantly improved by feeding DL diets (P<0.01), with better live and carcass weight and higher muscle pH (P<0.001), which were positively correlated with the inclusion level of DL (P<0.001). However, no differences between the control and 4% BSFL diet were observed for the performance parameters mentioned above. Moreover, all birds under our experimental setting exhibited a comparable feed conversion ratio (FCR) and were in a healthy status as indicated by the meat traits and haematological indexes within normal physiological ranges. Collectively, findings in this study provide theoretical basis for the further exploitation of Drosophila as potential dietary ingredients for feed production in order to meet the food challenge in the future.