Unc-51-like autophagy activating kinase 1 (ULK1)–autophagy-related 13 (ATG13) is the most upstream autophagy initiation complex that is phosphorylated by mammalian target-of-rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK) to induce autophagy in asynchronous conditions. However, their phospho-regulation and functions in mitosis and cell cycle remain unknown. Here we show that ULK1-ATG13 complex is differentially regulated throughout the cell cycle, especially in mitosis, in which both ULK1 and ATG13 are highly phosphorylated by the key cell cycle machinery cyclin-dependent kinase 1 (CDK1)/cyclin B. Combining mass spectrometry and site-directed mutagenesis, we found that CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression. Moreover, double knockout (DKO) of ULK1 and ATG13 could block cell cycle progression and significantly decrease cancer cell proliferation in cell line and mouse models. Our results not only bridge the mutual regulation between the core machinery of autophagy and mitosis but also illustrate the positive function of ULK1-ATG13 and their phosphorylation by CDK1 in mitotic autophagy regulation.

Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that dopamine receptors D2 and D3 (D2-like family) are positive regulators of autophagy, while dopamine receptors D1 and D5 (D1-like family) are negative regulators. Furthermore, dopamine and ammonia, the two reported endogenous ligands of dopamine receptors, both can induce dopamine receptor internalization and degradation. In addition, we found that AKT (protein kinase B)-mTOR (mechanistic target of rapamycin) and AMPK (AMP-activated protein kinase) pathways are involved in DRD3 (dopamine receptor D3) regulated autophagy. Moreover, autophagy machinery perturbation inhibited DRD3 degradation and increased DRD3 oligomer. Therefore, our study investigated the functions and mechanisms of dopamine receptors in autophagy regulation, which not only provides insights into better understanding of some dopamine receptor-related neurodegeneration diseases, but also sheds light on their potential treatment in combination with autophagy or mTOR pathway modulations.

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults, with an unfavourable outcome and a high rate of recurrence due to its heterogeneity. Dysregulation of fatty acid metabolism plays a crucial role in the development of several tumours. However, the value of fatty acid metabolism (FAM) in the progression of AML remains unclear. In this study, we obtained RNA sequencing and corresponding clinicopathological information from the TCGA and GEO databases. Univariate Cox regression analysis and subsequent LASSO Cox regression analysis were utilized to identify prognostic FAM-related genes and develop a potential prognostic risk model. Kaplan-Meier analysis was used for prognostic significances. We also performed ROC curve to illustrate that the risk model in prognostic prediction has good performance. Moreover, significant differences in immune infiltration landscape were found between high-risk and low-risk groups using ESTIMATE and CIBERSOT algorithms. In the end, differential expressed genes (DEGs) were analyzed by gene set enrichment analysis (GSEA) to preliminarily explore the possible signaling pathways related to the prognosis of FAM and AML. The results of our study may provide potential prognostic biomarkers and therapeutic targets for AML patients, which is conducive to individualized precision therapy.

Autophagy is a highly conserved pathway that mediates bulk degradation of cellular components in lysosomes/vacuoles and plays an important role in filamentous fungi by impacting growth, morphology and development. However, in leaf rust, the role of autophagy is poorly understood. In this study, we identified the structure of autophagy in leaf rust infection structures by using transmission electron microscopy (TEM). The results suggest that autophagy can be strongly induced in the haustorium mother cell (HMC) but did not occur in other special infection structures, such as the appressorium, substomatal vesicle and haustorial. Applying the autophagy inhibitor 3-mehyladenine (3-MA) to leaf rust resulted in significant arrest of mycelial growth and delays in leaf rust infection. These results suggest that autophagy can be induced in HMC and is important for fungal infection of wheat. This research will help us to expand our understanding of the physiological functions of autophagy in filamentous fungi.

ULK1-ATG13 is the most upstream autophagy initiation complex that is phosphorylated by mTORC1 and AMPK to induce autophagy in asynchronous conditions. However, the phospho-regulation and function of ULK1-ATG13 in mitosis and cell cycle remains unknown. Here we show that ULK1-ATG13 complex is differentially regulated throughout the cell cycle. Notably, in mitosis, both ULK1 and ATG13 are highly phosphorylated by CDK1/cyclin B, the key cell cycle machinery. Combining mass spectrometry and site-directed mutagenesis, we found that CDK1-induced ULK1-ATG13 phosphorylation positively regulates mitotic autophagy and Taxol chemosensitivity, and some phosphorylation sites occur in cancer patients. Moreover, double knockout of ULK1 and ATG13 could block cell cycle progression and significantly decrease cancer cell proliferation in cell line and mouse models. Our results not only bridge the mutual regulation between the core machineries of autophagy and mitosis, illustrate the mitotic autophagy regulation mechanism, but also provide ULK1-ATG13 as potential targets for cancer therapy.

Diffuse large B-cell lymphoma (DLBCL) is a challenging disease owing to its biological heterogeneity and variable outcomes. Single-nucleotide polymorphisms (SNPs) can significantly influence tumor susceptibility and prognosis. However, the clinical relevance of lipid metabolism-related SNPs in DLBCL remains unclear. We detected ten SNPs from eight genes related to lipid metabolism in 148 patients with DLBCL and 230 healthy controls. We examined the correlations between these SNPs and susceptibility, clinical features, and prognosis of patients with DLBCL. Our results indicated that PRKAG2 rs2727572 was associated with susceptibility to DLBCL, suggesting a potential role in disease occurrence. CPT2 rs1799822 was related to the Ann Arbor stage, whereas CYP19A1 rs10046 was associated with the risk stratification. FABP1 rs2197076 was correlated with treatment response, particularly the complete remission rate following chemotherapy. Furthermore, different genotype frequencies of CES1 rs8192950 were associated with survival, indicating its potential value for prognostic stratification. These results suggest that lipid metabolism-related SNPs may influence the pathogenesis and progression of DLBCL. However, this study is limited by sample size and the lack of an independent validation cohort. In conclusion, our findings provide novel insights that may inform future functional studies and therapeutic exploration in DLBCL.