Dataset Information

Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I.

ABSTRACT: Mitochondrial complex I (NADH:ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30-37 degrees C. The active/deactive transition could play an important role in the regulation of complex I activity. It has been suggested recently that complex I may become modified by S-nitrosation under pathological conditions during hypoxia or when the nitric oxide:oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only in the deactive form of the enzyme. By selective fluorescence labeling and proteomic analysis, we have identified this residue as cysteine-39 of the mitochondrially encoded ND3 subunit of bovine heart mitochondria. Cysteine-39 is located in a loop connecting the first and second transmembrane helix of this highly hydrophobic subunit. We propose that this loop connects the ND3 subunit of the membrane arm with the PSST subunit of the peripheral arm of complex I, placing it in a region that is known to be critical for the catalytic mechanism of complex I. In fact, mutations in three positions of the loop were previously reported to cause Leigh syndrome with and without dystonia or progressive mitochondrial disease.

SUBMITTER: Galkin A

PROVIDER: S-EPMC2475694 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I.

Galkin Alexander A Meyer Björn B Wittig Ilka I Karas Michael M Schägger Hermann H Vinogradov Andrei A Brandt Ulrich U

The Journal of biological chemistry 20080523 30

Mitochondrial complex I (NADH:ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30-37 degrees C. The active/deactive transition could play an important role in the regulation of complex I activity. It has been suggested recently that complex I may become modified by S-nitrosation under pathological conditions during hypoxia or when the nitric oxide:oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only in the deactiv ...[more]

PMID: 18502755

Similar Datasets

Project description:BackgroundThe prevalence of diabetic cognitive impairment (DCI) is significant, some studies have shown that it is related to mitochondrial respiratory chain homeostasis, but the specific mechanism is not clear. 2-hydroxyisobutyric acid (2-HIBA) is a novel short-chain fatty acid with potential applications in the treatment of metabolic diseases because it can regulate mitochondrial disorders. Our aim was to explore a novel mechanism of action for 2-HIBA in the treatment of DCI in mitochondrial respiratory chain homeostasis.MethodsMetabolic substances and differentially active metabolic pathways in the serum of diseased mice were identified based on multi-omics analysis. The nanoLC-Obitrap-MS technology was utilized to detect the content of selected small molecules with differential metabolic activity in the hippocampus and mitochondria of mice to evaluate their permeability through the blood-brain barrier (BBB) and outer mitochondrial membrane. A combination of behavioral, proteomic, and molecular biology approaches was used to explore specific regulatory mechanisms and identify potential pharmacological targets. Additionally, using techniques such as protein thermal shift, drug affinity responsive target stability (DARTS), hydrolase stability, and surface plasmon resonance (SPR) experiments, we demonstrated the direct binding effects of small molecule metabolites with protein targets.Results2-HIBA was found to directly ameliorate cognitive dysfunction in db/db mice by penetrating the blood-brain barrier and reversing the decrease in the protein content of NADH dehydrogenase 3 (MT-ND3) in the hippocampus through direct binding to ND3. This action helps maintain the stability of NAD+/NADH and regulate the mitochondrial respiratory chain balance. Furthermore, a combined medication plant agonist of 2-HIBA can enhance the expression of MT-ND3, thereby improving cognitive dysfunction in mice.ConclusionMT-ND3 is a crucial target for improving diabetic cognitive dysfunction, and 2-HIBA can directly bind to the MT-ND3 protein to alleviate the functional impairment of the mitochondrial respiratory chain in mice to treat DCI.

Dataset Information

Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I.

Publications

Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets