A5049345951- Mitochondrial Function and Pathology
- Biotin and Related Studies
- Click Chemistry and Applications
- RNA regulation and disease
- ATP Synthase and ATPases Research
- Heat shock proteins research
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Adipose Tissue and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Pancreatic function and diabetes
- Coenzyme Q10 studies and effects
- Apelin-related biomedical research
- Renal cell carcinoma treatment
- Multiple and Secondary Primary Cancers
- Epigenetics and DNA Methylation
- Medicinal Plants and Neuroprotection
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Pluripotent Stem Cells Research
- SARS-CoV-2 and COVID-19 Research
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
Seoul National University
2018-2025
Stanford University
2023-2025
Ulsan National Institute of Science and Technology
2020-2021
Significance Most of the thousands proteins that comprise a human cell have specific subcellular localization patterns essential for their function. “Proximity labeling” (PL) is method mapping endogenous cellular on proteome-wide scale. To improve specificity and versatility PL, we developed split-TurboID, promiscuous biotinylating enzyme split into two inactive fragments. The fragments are coexpressed in cells brought together by drug, protein–protein interaction, or organelle contact to...
The mitochondria-associated membrane (MAM) has emerged as a cellular signaling hub regulating various processes. However, its molecular components remain unclear owing to lack of reliable methods purify the intact MAM proteome in physiological context. Here, we introduce Contact-ID, split-pair system BioID with strong activity, for identification live cells. Contact-ID specifically labeled proteins proximal contact sites endoplasmic reticulum (ER) and mitochondria, thereby identified 115...
The inner mitochondrial membrane (IMM) proteome plays a central role in maintaining physiology and cellular metabolism. Various important biochemical reactions such as oxidative phosphorylation, metabolite production, biogenesis are conducted by the IMM proteome, mitochondria-targeted therapeutics have been developed for proteins, which is deeply related various human metabolic diseases including cancer neurodegenerative diseases. However, topology of remains largely unclear because lack...
Mitochondria-ER membrane contact sites (MERCS) represent a fundamental ultrastructural feature underlying unique biochemistry and physiology in eukaryotic cells. The ER protein PDZD8 is required for the formation of MERCS many cell types, however, its tethering partner on outer mitochondrial (OMM) currently unknown. Here we identify OMM FKBP8 as using combination unbiased proximity proteomics, CRISPR-Cas9 endogenous tagging, Cryo-electron tomography, correlative light-electron microscopy....
Targeting proximity-labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice (MAX-Tg) expressing mitochondrial matrix-targeted ascorbate peroxidase. Comparative analysis of matrix proteomes from the muscle tissues showed differential enrichment proteins. We found that reticulon 4-interacting protein 1 (RTN4IP1), also known as optic atrophy-10, enriched in and an NADPH oxidoreductase. Interactome vitro...
Dysregulated iron or Ca
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in human cells by interacting with host factors following infection. To understand the virus and interactome proximity, we introduce a super-resolution proximity labeling (SR-PL) method "plug-and-playable" PL enzyme, TurboID-GBP (GFP-binding nanobody protein), apply it for mapping of SARS-CoV-2 ORF3a membrane protein (M), which generates highly perturbed endoplasmic reticulum (ER) structures. Through SR-PL analysis...
Mitochondria-ER membrane contact sites (MERCS) represent a fundamental ultrastructural feature underlying unique biochemistry and physiology in eukaryotic cells. The ER protein PDZD8 is required for the formation of MERCS many cell types, however, its tethering partner on outer mitochondrial (OMM) currently unknown. Here we identified OMM FKBP8 as using combination unbiased proximity proteomics, CRISPR-Cas9 endogenous tagging, Cryo-Electron Microscopy (Cryo-EM) tomography, correlative...
Abstract Ubiquitin‐specific protease 4 (USP4) is highly overexpressed in colon cancer and acts as a potent protooncogenic protein by deubiquitinating β‐catenin. However, its prominent roles tumor formation migration cells are not fully understood enzyme (DUB) activity on Thus, we investigated an additional role of USP4 cancer. In this study, identified cortactin (CTTN), actin‐binding involved the regulation cytoskeleton dynamics potential prognostic marker for cancers, new cellular...
Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation linked to metabolic contexts. It thus of interests understand the traffic dynamics subcellular endosomal membranes are correlated regulatory roles metabolisms.
Mitochondrial thermogenesis is a process in which heat generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively fat cells with little knowledge on how may act beyond energy expenditure. Here, we highlight exothermic oxygen reduction reaction (ΔHf° = −286 kJ/mol) main source of protonophore-induced thermogenesis, and this conducted to other cellular organelles, including nucleus. As result, reached...
Abstract Proximity labeling (PL) catalyzed by promiscuous enzymes such as TurboID have enabled the proteomic analysis of subcellular regions difficult or impossible to access conventional fractionation-based approaches. Yet some cellular regions, organelle contact sites, remain out reach for current PL methods. To address this limitation, we split enzyme into two inactive fragments that recombine when driven together a protein-protein interaction membrane-membrane apposition. At endoplasmic...
Abstract Adapted oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle activations are essential tumor microenvironments for abnormal energy consumption to acquire malignancy drug resistance during cancer development progression. To elucidate the molecular mechanism related mitochondrial metabolic dynamics in glioblastoma (GBM), a longitudinal GBM orthotopic mouse model with acquired bevacizumab is established. The proteomic analysis results show that OXPHOS, TCA, calcium...
Summary The endomembrane reticulum (ER) is largely reorganized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 ORF3a and membrane (M) protein expression affects ER-derived structures including cubic double vesicles in coronavirus-infected cells; however, the molecular mechanisms underlying ER remodeling remain unclear. We introduced a “plug playable” proximity labeling tool (TurboID-GBP) for interactome mapping of GFP-tagged M proteins. Through mass spectrometric...
Abstract Targeting proximity labeling enzymes to specific cellular locations is a viable strategy for profiling subcellular proteomes. Here, we generated transgenic mice expressing mitochondrial matrix-targeted ascorbate peroxidase (MAX-Tg) analyze tissue-specific matrix Desthiobiotin-phenol of muscle tissues from MAX-Tg allowed efficient mitochondrial-localized proteins in these tissues. Comparative analysis proteomes revealed differential enrichment related energy production between...
Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) plays a central role in microglial biology and the pathogenesis of Alzheimer’s disease (AD). Besides DNAX-activating protein 12 (DAP12), communal adaptor for TREM2 many other receptors, cellular interactors remain largely elusive. We employed ‘proximity labeling’ approach using biotin ligase, TurboID, mapping protein–protein interactions live mammalian cells. discovered novel TREM2-proximal proteins with diverse functions,...
Abstract Mitochondrial thermogenesis is a process in which heat generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively fat cells, with little knowledge on how may act beyond energy expenditure. Here, we highlighted exothermic oxygen reduction reaction (ΔHf° = -285 kJ/mol) main source of protonophore-induced and this was conducted to other cellular organelles, including nuclei. As result, reached...
Abstract Background Microglia mediate key functions in inflammation and phagocytic clearance central to Alzheimer’s disease (AD). Semaphorins their receptors, plexins neuropilins, are best known for role axon guidance, but emerging roles include the regulation of innate immunity. Semaphorin receptors highly expressed microglia, including those encoded by AD risk genes discovered through genome‐wide association studies (e.g. PLXNA4 PLCγ2). We investigate function semaphorin 6D (Sema6D)...
Summary Dysregulated iron or Ca 2+ homeostasis has been reported in Parkinson’s disease (PD) models. Here we discover a connection between these two metals at the mitochondria. Elevation of levels causes inward mitochondrial overflow, through an interaction Fe with Mitochondrial Calcium Uniporter. In PD neurons, accumulation-triggered influx across surface leads to spatially confined elevation outer membrane, which is subsequently sensed by Miro1, -binding protein. A Miro1 blood test...
The endomembrane reticulum (ER) is largely reorganized by SARS-CoV-2 infection, however, detailed molecular mechanisms of ER remodeling the virus are still not fully understood. Here, we introduce a "plug and playable" proximity labeling tool (TurboID-GBP) for interactome mapping GFP-tagged ORF3a membrane (M) proteins SARS-CoV-2. Through mass spectrometric identification biotinylated lysine residue (K+226 Da) on viral using TurboID, 117 191 were robustly determined as interactomes M,...