Eukaryotic cells frequently experience fluctuations of the external and internal environments, such as changes in nutrient, energy and oxygen sources, and protein folding status, which, after reaching a particular threshold, become a type of stress. Cells develop several ways to deal with these various types of stress to maintain homeostasis and survival. Among the cellular survival mechanisms, autophagy is one of the most critical ways to mediate metabolic adaptation and clearance of damaged organelles. Autophagy is maintained at a basal level under normal growing conditions and gets stimulated by stress through different but connected mechanisms. In this review, we summarize the advances in understanding the autophagy regulation mechanisms under multiple types of stress including nutrient, energy, oxidative, and ER stress in both yeast and mammalian systems.

The rising popularity of smartphone health applications (apps) offers great potential for facilitating pediatric weight management. Pediatric providers can determine health interventions for young patients with excess weight. We surveyed 51 pediatric providers at a Midwest academic medical institution and found that 78% thought currently available resources were not sufficient for pediatric weight management. In all, 76% of respondents reported use of at least one smartphone health app for their personal health. The quality of pediatric providers’ experiences with their favorite app was strongly associated with their willingness to recommend the app to their patients ( P < .001), but few of them have made such a recommendation in practice, mainly due to the lack of either personal knowledge about health apps or about evidence-based health apps for pediatric weight management. Moreover, respondents shared ideas about qualities for an effective health app, which shed new light on developing apps specifically for adolescents with excess weight.

The aim of this study was to investigate the correlation of expression of IGF1R‐RACK1‐STAT3 and Bcl‐xl in nasopharyngeal carcinoma (NPC) with the clinicopathological features and the prognosis of NPC. Our study selected 215 NPC tissues and 178 chronic nasopharyngitis tissues (control group). Positive expression rates of IGF1R, RACK1, STAT3, and Bcl‐xl were tested by immunohistochemical method, and expression of IGF1R, RACK1, STAT3, Bcl‐xl, Bcl‐2, and Bax by western blotting. Correlation of IGF1R, RACK1, STAT3, and Bcl‐xl with the clinicopathological features of NPC was analyzed. The correlation among those four expression was analyzed by Spearman. The survival of NPC and independent factors of prognosis were tested by Kaplan‐Meier and COX proportional hazards model respectively. The NPC group had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl‐xl, and elevated expression of IGF1R, RACK1, STAT3, Bcl‐xl, Bcl‐2, and Bax. The lymph node metastasis (LNM) group had higher positive expression rates of IGF1R and RACK1 when compared with the non‐LNM group. Patients with stage III and IV had higher positive expression rates of IGF1R, RACK1, STAT3, and Bcl‐xl. There was positive correlation between expression of IGF1R and RACK1, STAT3. Such correlation was found between RACK1 and STAT3. Patients with negative expression of IGF1R, RACK1, STAT3, and Bcl‐xl had higher survival rates. The risky factors of poor prognosis of NPC were positive expression of IGF1R, RACK1, STAT3 and Bcl‐xl, and LNM. IGF1R‐RACK1‐STAT3 and Bcl‐xl expression correlated with the clinicopathological features and poor prognosis of NPC.

Although KRAS-driven tumors exhibit elevated macroautophagy/autophagy, the extent to which this process diverges from canonical regulatory pathways has not been well characterized. In a recent study published in Cell Research, Wang et al. unveil a novel form of non-canonical autophagy driven by oncogenic RAS mutations, which they termed RAS-induced non-canonical autophagy via ATG8ylation (RINCAA). This pathway operates through a unique MAPK/p38-ULK1-PI4KB axis, diverging significantly from canonical starvation-induced autophagy. The research not only elucidates a new regulatory mechanism but also identifies a potential, highly specific therapeutic target for RAS-mutant cancers.Abbreviations: PI4KB, phosphatidylinositol 4-kinase beta; PtdIns4P, phosphatidylinositol-4-phosphate; RINCAA, RAS-induced non-canonical autophagy via Atg8ylation; ULK1, unc-51 like autophagy activating kinase 1; WIPI2, WD repeat domain phosphoinositide-interacting protein 2.

Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the upregulation of autophagy and vacuole proteins involved in recycling, but also result in the downregulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Downregulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.