ArticleRedox biology2014
Defective mitophagy driven by dysregulation of rheb and KIF5B contributes to mitochondrial reactive oxygen species (ROS)-induced nod-like receptor 3 (NLRP3) dependent proinflammatory response and aggravates lipotoxicity.
Article in Redox biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 86 citations in OpenAlex.
- Regulation of Innate Immune Signaling by Autophagy.International journal of molecular sciences · 2026Review
- Dapansutrile preserves pancreatic beta-cell function by regulating insulin vesicle membrane fusion and mitochondrial homeostasis.Diabetes, obesity & metabolism · 2026Article
- Roles of mitochondrial complexes in non-alcoholic fatty liver disease.Frontiers in molecular biosciences · 2026Review
- Human OPN-derived peptide SV prevents BPD model through interacting with KIF5B to repair mitochondrial damage and inhibit apoptosis.iScience · 2025Article
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- Recent advances in natural polysaccharides for type 2 diabetes management: sources, structural characteristics, and mechanistic insights.Frontiers in pharmacology · 2025Review
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- Rooibos tea-in the cross fire of ROS, mitochondrial dysfunction and loss of proteostasis-positioned for healthy aging.Biogerontology · 2023Review
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- The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases.Cell & bioscience · 2022Review
- miR-155-5p in Extracellular Vesicles Derived from Choroid Plexus Epithelial Cells Promotes Autophagy and Inflammation to Aggravate Ischemic Brain Injury in Mice.Oxidative medicine and cellular longevity · 2022Article
- Identification of Potential Diagnoses Based on Immune Infiltration and Autophagy Characteristics in Major Depressive Disorder.Frontiers in genetics · 2022Article
- Lipid regulation of NLRP3 inflammasome activity through organelle stress.Trends in immunology · 2021Review
- Mitochondrial Dysfunction and Mitophagy Closely Cooperate in Neurological Deficits Associated with Alzheimer's Disease and Type 2 Diabetes.Molecular neurobiology · 2021Review
- Review
- Structural and Functional Remodeling of Mitochondria in Cardiac Diseases.International journal of molecular sciences · 2021Review
- Ferulic acid alleviates lipotoxicity-induced hepatocellular death through the SIRT1-regulated autophagy pathway and independently of AMPK and Akt in AML-12 hepatocytes.Nutrition & metabolism · 2021Article
- The Role of the Interplay Between Autophagy and NLRP3 Inflammasome in Metabolic Disorders.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-fat diet (HFD) and inflammation are the key contributors to insulin resistance and type 2 diabetes (T2D). Previous study shows fatty acid-induced accumulation of damaged, reactive oxygen species (ROS)-generating mitochondria, and this in turn activates the NLRP3 inflammasome interference with insulin signaling. Our previous research shows NLRP3 inflammasome activation signal originates from defects in autophagy. Yet how the fatty acid related to mitophagy alteration leads to the activation of NLRP3-ASC inflammasome has not been considered. Here we demonstrated that palmitate (PA) induced mitophagy deficiency, leading to damaged mitochondrion as characterized by mito-ROS production and loss of membrane potential. Antioxidant APDC or Ca(2+) signaling inhibitor Nifedipine blocked PA-induced NLRP3 inflammasome activation. Further, we provided evidences that PA reduced the expression of Ras homolog enriched in brain (Rheb) and disrupted Rheb recruitment to the mitochondrial outer membrane. In addition, sustained PA caused disassociation of kinesin family member 5B (KIF5B) from binding with mitochondria via Ca(2+)-dependent effects. Disruption of Rheb and KIF5B interaction with mitochondria blocked mitochondrial degradation along with IL-1β dependent insulin resistance, which was majorly attenuated by Rheb/KIF5B overexpression. In a consequence, defective mitophagy led to the accumulation of damaged-ROS-generating mitochondria, down pathway of NLRP3-ASC-Caspase 1 activation, and subsequently, insulin resistance. These findings provide insights into the association of inflammation, mitophagy and T2D.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.