Autophagy is a hallmark of aging, but it has not been exclusively targeted to attenuate aging-related physical dysfunction. Here, we combined Tat-Beclin1 and endurance training to determine its…

Autophagy is a hallmark of aging, but it has not been exclusively targeted to attenuate aging-related physical dysfunction. Here, we combined Tat-Beclin1 and endurance training to determine its effect on physical function domains in aged male mice. Mice were randomly divided into Control (N = 5), Tat-Beclin1 (TB, 15 mg/kg, 2×/week, N = 9), Exercise (Exe, 70%-maximal-running-speed, 3×/week, N = 9), and TB+Exe (N = 8) for 1 month in 23-month-old male C57BL/6J mice. Animals were assessed for grip...

Researchers have discovered that even a modest reduction in the protein BECLIN1 leads to a significant increase in inflammation in the gut, leading to further disease and complications over time.

Forschung der La Trobe University belegt: Reduziertes BECLIN1 schwächt die Darmbarriere und erhöht das Risiko für chronische Entzündungen.

Australian scientists have uncovered a crucial role for the protein BECLIN1 in maintaining gut integrity and defending against intestinal inflammation, offering fresh insights into conditions like

Cell Death & Disease - Impact of BECLIN1 haploinsufficiency on goblet cell function and susceptibility to colitis

Australian researchers have discovered that even a modest reduction in the protein BECLIN1 leads to a significant increase in gut inflammation, which can lead to further disease and complications over time.

Australian researchers have discovered that even a modest reduction in the protein BECLIN1 leads to a significant increase in gut inflammation, which can lead to further disease and complications over time.

In wild-type cells, FIPV infection recruits CLTC to nsp3, facilitates DMV biogenesis and block autophagic flux to promote viral replication. CLTC knockout impairs autophagosome nucleation by reducing Beclin1–ATG14 complex expression. This disrupts the formation of autophagic precursor membranes, thereby preventing their hijacking by nsp3 for DMV assembly. Partial restoration of autophagic flux severely restricts DMV biogenesis and viral replication. ABSTRACT Double-membrane vesicles (DMVs) are a hallmark of coronavirus replication, yet the host machinery governing their biogenesis remains poorly characterized, largely due to lack of tools for dynamic analysis. Here, we develop a live-cell imaging system using a recombinant virus that enables, for the first time, real-time visualization of DMV formation during authentic coronavirus infection. This system reveals the recruitment of the clathrin heavy chain (CLTC) to DMV assembly sites and demonstrates its essential role in diverse coronaviruses, but not in unrelated viruses. Notably, we define a previously unappreciated role of CLTC in viral replication organelle formation. Mechanistically, CLTC interacts with nonstructural protein 3 (nsp3) and is required for autophagosome nucleation by maintaining the core class III PI3K complex. The resulting CLTC-mediated autophagic precursor membranes are subsequently hijacked by nsp3 to form DMVs. Our study thereby establishes CLTC as a pivotal host factor for coronavirus replication and nominates both CLTC and the autophagosome nucleation pathway as promising antiviral targets.

Autophagy is a complex self-degradative process that recycles cytoplasmic components through lysosomal degradation, enabling cells to maintain homeostasis during stress and nutrient deprivation. Despite major advances in understanding the basic mechanisms of autophagy, important gaps remain in translating them to human diseases. This study investigated the metabolic fingerprints and footprints of two mechanistically different autophagy inducers, Torin1 (mTOR-dependent) and Tat-Beclin1 (mTOR-independent), in mouse embryonic fibroblasts (MEF). Multi-platform untargeted metabolomics and lipidomics analyses were performed at 3 and 18 h exposure to elucidate both intracellular and extracellular metabolic changes using liquid chromatography–high-resolution mass spectrometry coupled to drift tube ion mobility, complemented by [13C]-glucose tracing. Torin1 exposure caused downregulation of TCA cycle intermediates, accumulation of purine degradation products, enhanced phospholipid catabolism, and triglycerides’ enrichment. In contrast, Tat-Beclin1 preserved central carbon metabolism, promoted recovery of glutathione levels, and redirected diglycerides toward the biosynthesis of polyunsaturated phosphocholines (PC) and C18-containing phosphoethanolamines (PE). Despite these compound-specific responses, several common alterations were observed, including downregulation of ceramides, upregulation of ether-linked PEs, consistent enrichment of PC O-12:0_16:0, lyso-PE 22:6, PC 16:0_20:4, PC 16:0_22:5, and depletion of PE 32:1, PE 34:2, and PE 38:6, along with secretion of unsaturated fatty acids and uptake of sphingomyelin 35:1;O2 and cytosine from the extracellular compartment. Together, these results show that Torin1 and Tat-Beclin1 trigger distinct yet partly overlapping metabolic programs. The metabolic signatures identified here provide reference profiles for future mechanistic studies and highlight candidate biomarkers that may support early functional evaluation of autophagy modulators in disease-relevant settings. Graphical abstract

PRRS is one of the major diseases affecting the global swine industry. Infection with PRRSV can cause respiratory disease in pigs of all ages and reproductive disorders in sows. Therefore, understanding the interaction between PRRSV and host factors may help to develop new antiviral strategies against PRRSV. We found that PRRSV Nsp4 was important for nuclear export of TRIM28 in a CRM1-dependent manner during PRRSV infection. TRIM28 in the cytoplasm increases the formation of VPS34-Beclin1 complex by interacting with Vps34, further initiating autophagy. Hence, our study reveals a novel mechanism of PRRSV-mediated autophagy and provides valuable information for further understanding the pathogenesis of PRRS, which might contribute to the development of novel antiviral drugs.