A5076458250- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Calcium signaling and nucleotide metabolism
- Cellular transport and secretion
- Pancreatic function and diabetes
- Polyamine Metabolism and Applications
- Mitochondrial Function and Pathology
- Sirtuins and Resveratrol in Medicine
- Lipid metabolism and biosynthesis
- Studies on Chitinases and Chitosanases
- Fermentation and Sensory Analysis
- Ubiquitin and proteasome pathways
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Plant Gene Expression Analysis
- Psychological and Temporal Perspectives Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Healthcare professionals’ stress and burnout
- Plant and Fungal Interactions Research
- Phagocytosis and Immune Regulation
- Research in Cotton Cultivation
- Hops Chemistry and Applications
- Social and Cultural Dynamics
- RNA Research and Splicing
First Affiliated Hospital Zhejiang University
2020-2025
Chinese University of Hong Kong
2025
Zhejiang University
2017-2024
Tsinghua University
2012-2024
Obstetrics and Gynecology Hospital of Fudan University
2021
Second Affiliated Hospital of Zhejiang University
2018-2021
Center for Life Sciences
2012-2017
Peking University
2012-2017
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires
2012
Protein acetylation emerged as a key regulatory mechanism for many cellular processes. We used genetic analysis of Saccharomyces cerevisiae to identify Esa1 histone acetyltransferase required autophagy. further identified the autophagy signaling component Atg3 substrate Esa1. Specifically, K19 and K48 regulated by controlling Atg8 interaction lipidation Atg8. Starvation induced transient K19-K48 through spatial temporal regulation localization acetylase deacetylase Rpd3 on pre-autophagosomal...
Chaperone-mediated autophagy (CMA) is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases. However, mechanisms that regulate CMA are not fully understood. Here, using unbiased drug screening approaches, we discover Metformin, commonly first medication prescribed for type 2 diabetes, can induce CMA. We delineate mechanism induction by Metformin to be via activation TAK1-IKKα/β signaling leads phosphorylation Ser85 key...
Abstract There is increasing evidence that inducing neuronal mitophagy can be used as a therapeutic intervention for Alzheimer’s disease. Here, we screen library of 2024 FDA-approved drugs or drug candidates, revealing UMI-77 an unexpected activator. established BH3-mimetic MCL-1 and was developed to induce apoptosis in cancer cells. We found at sub-lethal doses, potently induces mitophagy, independent apoptosis. Our mechanistic studies discovered receptor directly binds LC3A. Finally, vivo...
Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense acids and connect the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at Ser86 phosphorylation site acetyltransferase Tip60 (Tip60 SA/SA ) display remarkably reduced body fat mass, females fail nurture pups adulthood due severely milk TAGs. Mechanistically, stimulate...
Abstract Acetylation of Atg3 regulates the lipidation protein Atg8 in autophagy. The molecular mechanism behind this important biochemical event remains to be elucidated. We describe first semi-synthesis homogeneous K19/K48-diacetylated through sequential hydrazide-based native chemical ligation. In vitro reconstitution experiments with semi-synthetic proteins confirm that acetylation can promote Atg8. find enhances its binding phosphatidylethanolamine-containing liposomes and endoplasmic...
Autophagy is essential for maintaining glucose homeostasis. However, the mechanism by which cells sense and respond to starvation induce autophagy remains incomplete. Here, we show that calcium serves as a fundamental triggering signal connects environmental sensing formation of initiation complex during starvation. Mechanistically, instigates release vacuolar into cytoplasm, thus activation Rck2 kinase. In turn, Rck2-mediated Atg11 phosphorylation enhances interactions with Bmh1/2 bound...
Mec1 plays an essential role in both the DNA damage response and glucose starvation–induced autophagy. We recently reported that regulates autophagy through its direct binding to Atg13. However, of Mec1’s kinase activity remains unclear. In this study, we demonstrate is required for by regulating phagophore assembly site (PAS) recruitment Atg9 vesicles. Mechanistic functional analyses identified as a phosphorylation substrate Mec1, with occurring at S35, T203, T243 sites. Mutations these...
This study investigated the longitudinal associations between academic and social adjustment mediating role of depressive symptoms among Chinese college freshmen using a three-wave design. A total 1183 (467 males; Mean age = 18.61 years at Wave 1) from eight universities participated in this study. Using cross-lagged panel analysis, results showed that predicted increases over time, but not vice versa. Academic adjustment, decreases time. Depressive worsened Longitudinal mediation analysis...
Macroautophagy/autophagy is an evolutionarily conserved intracellular degradation pathway that relies on vacuoles or lysosomes. Over 40 ATG genes have been identified in yeast cells as participants various types of autophagy, although these are non-essential. While some essential involved autophagy using temperature-sensitive strains, systematic research remains lacking. To address this, we established protein conditional library the auxin-inducible degron (AID) system. By introducing...
How energy deprivation induces macroautophagy/autophagy is not fully understood. Here, we show that Atg11, a receptor protein for cargo recognition in selective autophagy, required the initiation of glucose starvation-induced autophagy. Upon starvation, Atg11 facilitates interaction between Snf1 and Atg1, thus Snf1-dependent Atg1 activation. Phagophore assembly site (PAS) formation requires via its control association Atg17 with Atg29-Atg31. The binding Atg9 crucial recruiting vesicles to...
Atg11 is an adaptor protein required for the induction of selective autophagy via receptor binding. However, our understanding molecular mechanisms by which it regulates remains incomplete. Here, we show that phosphorylated Atg1. Rapamycin treatment or starvation conditions induced slower electrophoretic mobility in Atg1 kinase activity-dependent manner. Through vitro assays combined with mutagenesis, determined phosphorylates S949, S1057, and S1064 residues CC4 domain Atg11. Replacing three...
Mec1 is a DNA damage sensor, which performs an essential role in the response pathway and glucose starvation-induced autophagy. However, functions of autophagy remain unclear. In to starvation, forms puncta, are recruited mitochondria through adaptor protein Ggc1. Here, we show that puncta also contact phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis Atg13–Mec1 interaction revealed two previously unrecognized regions, M ec1- B inding R egion (MBR) on Atg13 A...
Macroautophagy/autophagy is essential for maintaining glucose homeostasis, but the mechanisms by which cells sense starvation and initiate autophagy are not yet fully understood. Recently, we reported that assembly of a Ca2+-triggered Snf1-Bmh1/Bmh2-Atg11 complex initiates in response to starvation. Our research reveals during starvation, efflux vacuolar Ca2+ increases cytoplasmic levels, activates protein kinase Rck2. Rck2-mediated phosphorylation Atg11 enhances its interaction with Bmh1...
Seeing is believing. The direct observation of GFP-Atg8 vacuolar delivery under confocal microscopy one the most useful end-point measurements for monitoring yeast macroautophagy/autophagy. However, manually labelling individual cells from large-scale sets images time-consuming and labor-intensive, which has greatly hampered its extensive use in functional screens. Herein, we conducted a time-course analysis nitrogen starvation-induced autophagy wild-type knockout mutants 35...
Mitochondria are highly dynamic organelles, which can form a network in cells through fusion, fission and tubulation. Its morphology is closely related to the function of mitochondria. The damaged mitochondria be removed by mitophagy. However, relationship between mitochondrial non-selective autophagy not fully understood. We found that fusion machinery, tubulation essential for energy deprivation-induced autophagy. In response glucose starvation, deletion proteins severely impaired...
Mounting evidence suggests that acetylation plays an important role in various biological processes including transcriptional regulation, DNA damage repair, cell cycle progression, aging, and glycolysis. It is increasingly recognized also regulates autophagy; for example, increasing the cellular level by treating cells with histone deacetylase (HDAC) inhibitors such as TSA can promote autophagy, knockdown of acetyltransferase KAT2B/p300 induces autophagy nutrient-rich conditions. Our goal to...