ArticleNeurochemistry international2016
Mild mitochondrial metabolic deficits by α-ketoglutarate dehydrogenase inhibition cause prominent changes in intracellular autophagic signaling: Potential role in the pathobiology of Alzheimer's disease.
Article in Neurochemistry international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.Aging and disease · 2025Review
- Parapyruvate Induces Neurodegeneration in C57BL/6JNarl Mice via Inhibition of the α-Ketoglutarate Dehydrogenase Complex.ACS omega · 2024Article
- Defective function of α-ketoglutarate dehydrogenase exacerbates mitochondrial ATP deficits during complex I deficiency.Redox biology · 2023Article
- The α-Ketoglutarate Dehydrogenase Complex as a Hub of Plasticity in Neurodegeneration and Regeneration.International journal of molecular sciences · 2022Review
- Metabolic Features of Brain Function with Relevance to Clinical Features of Alzheimer and Parkinson Diseases.Molecules (Basel, Switzerland) · 2022Review
- Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer's disease.Nature communications · 2022Article
- Suppression of a core metabolic enzyme dihydrolipoamide dehydrogenase (Genes & diseases · 2021Article
- Selective linkage of mitochondrial enzymes to intracellular calcium stores differs between human-induced pluripotent stem cells, neural stem cells, and neurons.Journal of neurochemistry · 2021Article
- Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Review
- Metabolomic Assays of Postmortem Brain Extracts: Pitfalls in Extrapolation of Concentrations of Glucose and Amino Acids to Metabolic Dysregulation In Vivo in Neurological Diseases.Neurochemical research · 2019Article
- Reduced FAK-STAT3 signaling contributes to ER stress-induced mitochondrial dysfunction and death in endothelial cells.Cellular signalling · 2017Article
- The α-ketoglutarate dehydrogenase complex in cancer metabolic plasticity.Cancer & metabolism · 2017Review
- Reductions in the mitochondrial enzyme α-ketoglutarate dehydrogenase complex in neurodegenerative disease - beneficial or detrimental?Journal of neurochemistry · 2016Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Brain activities of the mitochondrial enzyme α-ketoglutarate dehydrogenase complex (KGDHC) are reduced in Alzheimer's disease and other age-related neurodegenerative disorders. The goal of the present study was to test the consequences of mild impairment of KGDHC on the structure, protein signaling and dynamics (mitophagy, fusion, fission, biogenesis) of the mitochondria. Inhibition of KGDHC reduced its in situ activity by 23-53% in human neuroblastoma SH-SY5Y cells, but neither altered the mitochondrial membrane potential nor the ATP levels at any tested time-points. The attenuated KGDHC activity increased translocation of dynamin-related protein-1 (Drp1) and microtubule-associated protein 1A/1B-light chain 3 (LC3) from the cytosol to the mitochondria, and promoted mitochondrial cytochrome c release. Inhibition of KGDHC also increased the negative surface charges (anionic phospholipids as assessed by Annexin V binding) on the mitochondria. Morphological assessments of the mitochondria revealed increased fission and mitophagy. Taken together, our results suggest the existence of the regulation of the mitochondrial dynamism including fission and fusion by the mitochondrial KGDHC activity via the involvement of the cytosolic and mitochondrial protein signaling molecules. A better understanding of the link among mild impairment of metabolism, induction of mitophagy/autophagy and altered protein signaling will help to identify new mechanisms of neurodegeneration and reveal potential new therapeutic approaches.
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