ArticleRedox biology2023
Defective function of α-ketoglutarate dehydrogenase exacerbates mitochondrial ATP deficits during complex I deficiency.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- A Micropeptide Component of the OGDH Complex Modulates ATP Production in the TCA Cycle.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unveiling the pathogenesis and therapeutic strategies of Alzheimer's disease through cuproptosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- DLST-driven metabolic alterations link skin to blood glucose: A translational study from mouse to human.Molecular metabolism · 2026Article
- Restoring glucose metabolic homeostasis to attenuate ovarian aging: mechanisms and clinical prospects.Journal of ovarian research · 2026Review
- Characterization of aMolecular genetics and metabolism reports · 2026Article
- Succinylation: novel molecular mechanisms and prospects for targeted therapy in liver diseases.Frontiers in molecular biosciences · 2026Review
- Targeting cuproptosis for treatment and prognostic assessment in endometrial cancer.Cancer cell international · 2025Review
- An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.Nature communications · 2025Article
- Cystatin antibodies interfere with ovary development in Haemaphysalis doenitzi (Acari: Ixodidae).PLoS neglected tropical diseases · 2025Article
- The metabolic-epigenetic interface: lysine succinylation orchestrates bidirectional crosstalk in neurodegenerative disorders.Frontiers in neurology · 2025Review
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Quantification of the immunometabolite protein modifications S-2-succinocysteine and 2,3-dicarboxypropylcysteine.American journal of physiology. Endocrinology and metabolism · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The NDUFS4 knockout (KO) mouse phenotype resembles the human Complex I deficiency Leigh Syndrome. The irreversible succination of protein thiols by fumarate is increased in select regions of the NDUFS4 KO brain affected by neurodegeneration. We report that dihydrolipoyllysine-residue succinyltransferase (DLST), a component of the α-ketoglutarate dehydrogenase complex (KGDHC) of the tricarboxylic acid (TCA) cycle, is succinated in the affected regions of the NDUFS4 KO brain. Succination of DLST reduced KGDHC activity in the brainstem (BS) and olfactory bulb (OB) of KO mice. The defective production of KGDHC derived succinyl-CoA resulted in decreased mitochondrial substrate level phosphorylation (SLP), further aggravating the existing oxidative phosphorylation (OXPHOS) ATP deficit. Protein succinylation, an acylation modification that requires succinyl-CoA, was reduced in the KO mice. Modeling succination of a cysteine in the spatial vicinity of the DLST active site or introduction of succinomimetic mutations recapitulates these metabolic deficits. Our data demonstrate that the biochemical deficit extends beyond impaired Complex I assembly and OXPHOS deficiency, functionally impairing select components of the TCA cycle to drive metabolic perturbations in affected neurons.
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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.