ArticleAntioxidants & redox signaling2017
Succination of Protein Disulfide Isomerase Links Mitochondrial Stress and Endoplasmic Reticulum Stress in the Adipocyte During Diabetes.
Article in Antioxidants & redox signaling, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Expansion of Germline Variants in Primary Hyperparathyroidism: Fumarate Hydratase Deficiency as a Cause of Parathyroid Adenomas.Endocrine pathology · 2026Observational
- Excessive or sustained endoplasmic reticulum stress: one of the culprits of adipocyte dysfunction in obesity.Therapeutic advances in endocrinology and metabolism · 2024Review
- Defective function of α-ketoglutarate dehydrogenase exacerbates mitochondrial ATP deficits during complex I deficiency.Redox biology · 2023Article
- Sulfenylation links oxidative stress to protein disulfide isomerase oxidase activity and thrombus formation.Journal of thrombosis and haemostasis : JTH · 2023Article
- Specific Post-Translational Modifications of VDAC3 in ALS-SOD1 Model Cells Identified by High-Resolution Mass Spectrometry.International journal of molecular sciences · 2022Article
- RIG-I Deficiency Promotes Obesity-Induced Insulin Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Article
- ERO1-PDI Redox Signaling in Health and Disease.Antioxidants & redox signaling · 2021Review
- Oxidative Cysteine Modification of Thiol Isomerases in Thrombotic Disease: A Hypothesis.Antioxidants & redox signaling · 2021Review
- Fumarate and oxidative stress synergize to promote stability of C/EBP homologous protein in the adipocyte.Free radical biology & medicine · 2020Article
- Succination of Protein Thiols in Human Brain Aging.Frontiers in aging neuroscience · 2020Review
- Mechanistic Connections between Endoplasmic Reticulum (ER) Redox Control and Mitochondrial Metabolism.Cells · 2019Review
- Identification of Novel Protein Targets of Dimethyl Fumarate Modification in Neurons and Astrocytes Reveals Actions Independent of Nrf2 Stabilization.Molecular & cellular proteomics : MCP · 2019Article
- Inhibition of protein disulfide isomerase in glioblastoma causes marked downregulation of DNA repair and DNA damage response genes.Theranostics · 2019Article
- Review
- Identification of a metabolic disposal route for the oncometaboliteThe Journal of biological chemistry · 2018Article
- Analysis of fumarate-sensitive proteins and sites by exploiting residue interaction networks.Amino acids · 2018Article
- Post-Translational Modification of Cysteines: A Key Determinant of Endoplasmic Reticulum-Mitochondria Contacts (MERCs).Contact (Thousand Oaks (Ventura County, Calif.))Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
aimsProtein succination by fumarate increases in the adipose tissue of diabetic mice and in adipocytes matured in high glucose as a result of glucotoxicity-driven mitochondrial stress. The endoplasmic reticulum (ER) oxidoreductase protein disulfide isomerase (PDI) is succinated in adipocytes that are matured in high glucose, and in this study we investigated whether succination would alter PDI oxidoreductase activity, directly linking mitochondrial stress and ER stress.
resultsProtein succination and the ER stress marker C/EBP homologous protein (CHOP) were diminished after pharmaceutical targeting of mitochondrial stress with the chemical uncoupler niclosamide in adipocytes matured in high-glucose concentrations. PDI was succinated by fumarate on both CXXC-containing active sites, contributing to reduced enzymatic activity. Succinated PDI decreased reductase activity in adipocytes matured in high glucose, and in db/db epididymal adipose tissue, in association with increased levels of CHOP. PDI succination was increased in fumarase knockdown adipocytes, leading to reduced PDI oxidoreductase activity, increased CHOP levels, and pro-inflammatory cytokine secretion, confirming the specific role of elevated fumarate levels in contributing to ER stress. In addition, PDI succination and ER stress were decreased, and PDI reductase activity was restored when exposure to chronic high glucose was limited, highlighting the importance of calorie restriction in the improvement of adipocyte metabolic function. INNOVATION: These experiments identify PDI succination as a novel biochemical mechanism linking altered mitochondrial metabolism to ER stress in the adipocyte during diabetes.
conclusionThe current study demonstrates that early biochemical changes in mitochondrial metabolism have important implications for the development of adipocyte stress. Antioxid. Redox Signal. 27, 1281-1296.
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