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.

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.

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

Hepatitis E virus (HEV) is a zoonotic pathogen that can infect pregnant women and cause adverse pregnancy outcomes, including miscarriage and preterm delivery. The previous study demonstrated that HEV genotype 3 (HEV-3) inhibits complete autophagic flux in both mouse placental tissue and human trophoblast cells (JEG-3), evidenced by reduced expression of ATG proteins (including LC3, Beclin1, ATG4B, ATG5, and ATG9A) and accumulation of p62. However, the specific regulatory pathway involved remains unclear. Thus, eukaryotic expression vectors for HEV open reading frames (ORFs) were constructed, and ORF2 and ORF3 proteins were transiently overexpressed in JEG-3 cells via liposome transfection. While both ORF2 and ORF3 significantly reduced LC3B protein levels (p < 0.01), only ORF2 induced p62 accumulation (p < 0.01), indicative of autophagic inhibition, which indicates that ORF2 was the key viral protein mediating autophagy suppression in JEG-3. The results of WB and RT-qPCR show that ORF2 suppressed the PI3K/Akt/mTOR pathway while enhancing nuclear translocation of TFEB (p < 0.01) and AMPK phosphorylation (p < 0.01), suggesting paradoxical activation of upstream autophagy regulators. Through co-transfection of mCherry-LC3 with ORF2, co-localization studies, and AlphaFold 3-based intermolecular interaction predictions, we proposed that ORF2 directly binds LC3B to block autophagosome formation. Finally, co-immunoprecipitation confirmed physical interaction between HEV ORF2 and LC3B, elucidating the molecular mechanism of HEV-induced autophagy suppression in trophoblasts. These findings reveal the molecular mechanism by which HEV inhibits autophagy leading to miscarriage in mice, providing new insights into HEV-induced reproductive damage.

Hepatitis E virus (HEV) is a zoonotic pathogen that can infect pregnant women and cause adverse pregnancy outcomes, including miscarriage and preterm delivery. The previous study demonstrated that HEV genotype 3 (HEV-3) inhibits complete autophagic flux in both mouse placental tissue and human trophoblast cells (JEG-3), evidenced by reduced expression of ATG proteins (including LC3, Beclin1, ATG4B, ATG5, and ATG9A) and accumulation of p62. However, the specific regulatory pathway involved remains unclear. Thus, eukaryotic expression vectors for HEV open reading frames (ORFs) were constructed, and ORF2 and ORF3 proteins were transiently overexpressed in JEG-3 cells via liposome transfection. While both ORF2 and ORF3 significantly reduced LC3B protein levels (p < 0.01), only ORF2 induced p62 accumulation (p < 0.01), indicative of autophagic inhibition, which indicates that ORF2 was the key viral protein mediating autophagy suppression in JEG-3. The results of WB and RT-qPCR show that ORF2 suppressed the PI3K/Akt/mTOR pathway while enhancing nuclear translocation of TFEB (p < 0.01) and AMPK phosphorylation (p < 0.01), suggesting paradoxical activation of upstream autophagy regulators. Through co-transfection of mCherry-LC3 with ORF2, co-localization studies, and AlphaFold 3-based intermolecular interaction predictions, we proposed that ORF2 directly binds LC3B to block autophagosome formation. Finally, co-immunoprecipitation confirmed physical interaction between HEV ORF2 and LC3B, elucidating the molecular mechanism of HEV-induced autophagy suppression in trophoblasts. These findings reveal the molecular mechanism by which HEV inhibits autophagy leading to miscarriage in mice, providing new insights into HEV-induced reproductive damage.

Protein kinase R-like endoplasmic reticulum kinase-phosphorylated adenylosuccinate lyase (ADSL) binds to Beclin1 upon lipid deprivation. ADSL-produced fumarate increases Beclin1 K117 dimethylation by ...

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 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

Protein kinase R-like endoplasmic reticulum kinase-phosphorylated adenylosuccinate lyase (ADSL) binds to Beclin1 upon lipid deprivation. ADSL-produced fumarate increases Beclin1 K117 dimethylation by ...

African swine fever (ASF) is a highly contagious viral disease that affects both domestic and wild p

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.