Genomic organization of the human complex I 13-kDa subunit gene NDUFA5

Tensing, Kristiina; Pata, Illar; Wittig, Ilka; Wehnert, Manfred; Metspalu, Andres

doi:10.1159/000015237

Cited by 6 publications

(3 citation statements)

References 10 publications

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“…The investigators identified two SNPs (rs12666974 and rs23779262) in the NDUFA5 gene which were associated with ASD. NDUFA5 encodes NADH–ubiquinone oxidoreductase 1 alpha subcomplex 5, an accessory subunit of complex I of the ETC [60]. Thus, such mutations could have consequences for complex I activity.…”

Section: The Genetic Link Between Mitochondrial Dysfunction and Aumentioning

confidence: 99%

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Griffiths

Levy

2017

Oxidative Medicine and Cellular Longevity

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Autism spectrum disorder (ASD), the fastest growing developmental disability in the United States, represents a group of neurodevelopmental disorders characterized by impaired social interaction and communication as well as restricted and repetitive behavior. The underlying cause of autism is unknown and therapy is currently limited to targeting behavioral abnormalities. Emerging studies suggest a link between mitochondrial dysfunction and ASD. Here, we review the evidence demonstrating this potential connection. We focus specifically on biochemical links, genetic-based associations, non-energy related mechanisms, and novel therapeutic strategies.

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Section: The Genetic Link Between Mitochondrial Dysfunction and Aumentioning

confidence: 99%

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Griffiths

Levy

2017

Oxidative Medicine and Cellular Longevity

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“…The IP fraction contains seven subunits (NDUFA5, NDUFS1–S6), all characterized at the cDNA level. Recently, the genomic organization of the NDUFA5 [Tensing et al, 1999] and NDUFS3 genes has been characterized [Procaccio et al, 2000]. Although the exact localization of two subunits, the nuclear‐encoded 17.2 kDa subunit and the mitochondrial‐encoded subunit ND6, is still unknown in the complex [Sazanov et al, 2000], the remaining proteins are all thought to be part of the HP fraction.…”

Section: Structure Of Human Complex Imentioning

confidence: 99%

Respiratory chain complex I deficiency

Triepels¹,

Heuvel

Trijbels³

et al. 2001

Am. J. Med. Genet.

165

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Oxidative phosphorylation disorders make a contribution of 1 per 10,000 live births in man, of which isolated complex I deficiency is frequently the cause. Complex I, or NADH:ubiquinone oxidoreductase, is the largest multi-protein enzyme complex of the mitochondrial electron transfer chain. In complex I deficiency, various clinical phenotypes have been recognized, often resulting in multi-system disorders with a fatal outcome at a young age. Recent advances in complex I deficiency, regarding clinical, biochemical, and molecular aspects are described. However, the genetic causes of about 60% of complex I deficiency remain unclear. As a consequence, further research will be needed to clarify the genetic defects in the remaining cases. Novel strategies in which interesting non-structural nuclear-encoded disease-causing genes may be found, as well as the molecular genetic composition of human complex I, are presented.

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“…NDUFA5, as a hydrophobic fraction of the mitochondrial complex I multisubunit enzyme, is believed to be not involved in catalysis, but participated in transferring electrons from NADH to the respiratory chain. 22,23 The expression of NDUFA5 was reduced in brains of autism patients, which might be attributed to mitochondrial dysfunction and impaired ATP synthesis. 24 Present study provided evidence that abnormal NDUFA5 expression was involved in the process of fatty liver disease.…”

Section: Ndufa5mentioning

confidence: 99%

Hepatocyte miR‐33a mediates mitochondrial dysfunction and hepatosteatosis by suppressing NDUFA5

Nie

et al. 2018

J Cellular Molecular Medi

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Emerging evidence suggests that microRNAs (miRNAs) are essential for metabolic haemostasis of liver tissues. Among them, miR‐33a is supposed to modulate the cholesterol export and fatty acid oxidation, but whether miR‐33a involves in the process of fatty liver disease is unclear. To disclose the hypothesis, we utilized miR‐33a mimic and antisense to explore their effects in primary hepatocytes or high‐fat diet (HFD)‐fed mice. Treatment with palmitic acid (PA) or HFD significantly increased the expression of miR‐33a in hepatocytes or liver tissues. In primary hepatocytes, miR‐33a mimic decreased mitochondrial function, including reduction of ATP production and oxygen consumption, whereas miR‐33a inhibition protected PA‐induced mitochondrial dysfunction. Interestingly, miR‐33a selectively suppressed mitochondrial complex I activity and protein expression, but not other complexes. Through bioinformatics prediction, we found miR‐33a directly targeted on the 3′‐UTR of NDUFA5. Dual‐luciferase reporter analysis further confirmed the direct suppression of miR‐33a on NDUFA5 expression. More importantly, administration of miR‐33a antisense could effectively restore HFD‐induced mitochondrial dysfunction through up‐regulation of NDUFA5 levels. Mice treated with miR‐33a antisense also exhibited improved liver function and structural disorders under obese status. Taken together, miR‐33a was an important mediator of hepatocyte mitochondrial function, and the therapeutic benefits implied miR‐33a antisense had the potential clinical application in combating the fatty liver disease.

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Genomic organization of the human complex I 13-kDa subunit gene NDUFA5

Cited by 6 publications

References 10 publications

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Evidence of Mitochondrial Dysfunction in Autism: Biochemical Links, Genetic‐Based Associations, and Non‐Energy‐Related Mechanisms

Respiratory chain complex I deficiency

Hepatocyte miR‐33a mediates mitochondrial dysfunction and hepatosteatosis by suppressing NDUFA5

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