Mitochondrial complex III stabilizes complex I in the absence of NDUFS4 to provide partial activity.
Publication year
2012Source
Human Molecular Genetics, 21, 1, (2012), pp. 115-20ISSN
Publication type
Article / Letter to editor
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Organization
Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
Biochemistry (UMC)
Journal title
Human Molecular Genetics
Volume
vol. 21
Issue
iss. 1
Page start
p. 115
Page end
p. 20
Subject
IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism; NCMLS 4: Energy and redox metabolismAbstract
Mitochondrial complex I (CI) is a multi-subunit enzyme that forms the major entry point of nicotinamide adenine dinucleotide (NADH) electrons into the respiratory chain. Mutations in the NDUFS4 gene, encoding an accessory subunit of this complex, cause a Leigh-like phenotype in humans. To study the nature and penetrance of the CI defect in different tissues, we investigated the role of NDUFS4 in mice with fatal mitochondrial encephalomyopathy, caused by a systemic inactivation of the Ndufs4 gene. We report that the absence of NDUFS4 in different mouse tissues results in decreased activity and stability of CI. This CI instability leads to an increased disconnection of electron influx of the NADH dehydrogenase module from the holo-complex. However, the formation of respiratory supercomplexes still allows formation of active CI in these Ndufs4 knock-out mice. These results reveal the importance of these supramolecular interactions not only for stabilization but also for the assembly of CI, which becomes especially relevant in pathological conditions.
This item appears in the following Collection(s)
- Academic publications [238426]
- Faculty of Medical Sciences [90358]
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