ArticleMolecular metabolism2020
Cyb5r3 links FoxO1-dependent mitochondrial dysfunction with β-cell failure.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Human β-Cell Dedifferentiation and Diabetes.Journal of diabetes · 2026Review
- Investigational treatments of β-cell failure and replacement.Diabetology international · 2026Review
- Modulation of PKCα/ETS1 by klotho restores CYB5R4-dependent mitochondrial function in proximal tubular epithelial cells to attenuate the progression of diabetic kidney disease.Cardiovascular diabetology · 2026Article
- Mitochondria in health and disease: cellular powerhouses, signaling centers, and drivers of dysfunction.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes.Experimental & molecular medicine · 2025Article
- Insulin resistance in type 2 diabetes mellitus.Nature reviews. Endocrinology · 2025Review
- β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects.The Journal of clinical endocrinology and metabolism · 2025Article
- Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science (New York, N.Y.) · 2025Article
- Electronic cigarette vape decreases nitric oxide bioavailability in vascular smooth muscle cells via increased cytoglobin-mediated metabolism.Free radical biology & medicine · 2025Article
- CYB5R3 functions as a tumor suppressor by inducing ER stress-mediated apoptosis in lung cancer cells via the PERK-ATF4 and IRE1α-JNK pathways.Experimental & molecular medicine · 2024Article
- Vitamin E/Coenzyme Q-Dependent "Free Radical Reductases": Redox Regulators in Ferroptosis.Antioxidants & redox signaling · 2024Review
- Cyb5r3 activation rescues secondary failure to sulfonylurea but not β-cell dedifferentiation.PloS one · 2024Article
- CYB5R3 in type II alveolar epithelial cells protects against lung fibrosis by suppressing TGF-β1 signaling.JCI insight · 2023Article
- Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failure.Nature communications · 2023Article
- FoxO1 as a tissue-specific therapeutic target for type 2 diabetes.Frontiers in endocrinology · 2023Review
- Reflections on the state of diabetes research and prospects for treatment.Diabetology international · 2023Review
- Ginsenoside Rb1 inhibits oxidative stress-induced ovarian granulosa cell injury through Akt-FoxO1 interaction.Science China. Life sciences · 2022Article
- Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator.The Journal of pathology · 2022Article
- FoxO transcription factors in mitochondrial homeostasis.The Biochemical journal · 2022Article
- Role of cytoglobin in cigarette smoke constituent-induced loss of nitric oxide bioavailability in vascular smooth muscle cells.Nitric oxide : biology and chemistry · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDiabetes is characterized by pancreatic β-cell dedifferentiation. Dedifferentiating β cells inappropriately metabolize lipids over carbohydrates and exhibit impaired mitochondrial oxidative phosphorylation. However, the mechanism linking the β-cell's response to an adverse metabolic environment with impaired mitochondrial function remains unclear.
methodsHere we report that the oxidoreductase cytochrome b5 reductase 3 (Cyb5r3) links FoxO1 signaling to β-cell stimulus/secretion coupling by regulating mitochondrial function, reactive oxygen species generation, and nicotinamide actin dysfunction (NAD)/reduced nicotinamide actin dysfunction (NADH) ratios.
resultsThe expression of Cyb5r3 is decreased in FoxO1-deficient β cells. Mice with β-cell-specific deletion of Cyb5r3 have impaired insulin secretion, resulting in glucose intolerance and diet-induced hyperglycemia. Cyb5r3-deficient β cells have a blunted respiratory response to glucose and display extensive mitochondrial and secretory granule abnormalities, consistent with altered differentiation. Moreover, FoxO1 is unable to maintain expression of key differentiation markers in Cyb5r3-deficient β cells, suggesting that Cyb5r3 is required for FoxO1-dependent lineage stability.
conclusionsThe findings highlight a pathway linking FoxO1 to mitochondrial dysfunction that can mediate β-cell failure.
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