Human NDUFS3 gene coding for the 30-kDa subunit of mitochondrial Complex I: genomic organization and expression

Procaccio, Vincent; Lescuyer, Pierre; Bourges, Ingrid; Beugnot, Réjane; Duborjal, H.; Depetris, Danielle; Mousson, B.; Montfort, Marie-France; Smeets, Hubert J.M.; Coo, I.F.M. de; Issartel, Jean-Paul

doi:10.1007/s003350010160

Cited by 12 publications

(4 citation statements)

References 9 publications

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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.

163

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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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Section: Structure Of Human Complex Imentioning

confidence: 99%

Respiratory chain complex I deficiency

Triepels¹,

Heuvel

Trijbels³

et al. 2001

Am. J. Med. Genet.

163

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“…As a catalytic subunit, it has been shown to play a vital role in the proper assembly of intact, functional complex I in the human mitochondrial respiratory chain. [14,15,16,17] Implications of complex I deficiency/ dysfunction in a variety of neurodegenerative disorders have been documented. [14,18,19,20] However, there is no published evidence for its role in cancer pathology.…”

Section: Introductionmentioning

confidence: 99%

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

Suhane

Berel

Ramanujan

2011

Biochemical and Biophysical Research Communications

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We present evidence for potential biomarker utility of a mitochondrial complex I subunit, (NDUFS3) in discriminating normal and highly invasive breast carcinoma specimens obtained from clinical patients. Besides being a robust indicator of breast cancer aggressiveness, NDUFS3 also shows clear signatures of a hypoxia/necrosis marker in invasive ductal carcinoma specimens. Statistically significant positive correlation was observed between nuclear grade and NDUFS3 expression level in the tumor specimens analyzed. We support these findings with a plausible mechanism involving mitochondrial complex I assembly defects and/or redox buffering induced mitochondrial dysfunction during the process of cancer cell transformation. From a clinical standpoint, this novel observation adds value in augmenting the current receptor-based biomarkers for better accuracy in diagnosis and predicting survival rate in patients with breast carcinoma.

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“… * Associated proteins that were also identified by the Fat1 TAP–MS screen. † Refs 41–66 are cited in this table. …”

Section: Extended Datamentioning

confidence: 99%

Control of mitochondrial function and cell growth by the atypical cadherin Fat1

Cao

Riascos-Bernal

Chinnasamy

et al. 2016

Nature

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Mitochondrial products such as ATP, reactive oxygen species, and aspartate are key regulators of cellular metabolism and growth. Abnormal mitochondrial function compromises integrated growth-related processes such as development and tissue repair1,2, as well as homeostatic mechanisms that counteract ageing and neurodegeneration3, cardiovascular disease4,5, and cancer6,7. Physiologic mechanisms that control mitochondrial activity in such settings remain incompletely understood. Here we show that the atypical Fat1 cadherin acts as a molecular ‘brake’ on mitochondrial respiration that regulates vascular smooth muscle cell (SMC) proliferation after arterial injury. Fragments of Fat1 accumulate in SMC mitochondria, and the Fat1 intracellular domain interacts with multiple mitochondrial proteins, including critical factors associated with the inner mitochondrial membrane. SMCs lacking Fat1 (Fat1KO) grow faster, consume more oxygen for ATP production, and contain more aspartate. Notably, expression in Fat1KO cells of a modified Fat1 intracellular domain that localizes exclusively to mitochondria largely normalizes oxygen consumption, and the growth advantage of these cells can be suppressed by inhibition of mitochondrial respiration, which suggest that a Fat1-mediated growth control mechanism is intrinsic to mitochondria. Consistent with this idea, Fat1 species associate with multiple respiratory complexes, and Fat1 deletion both increases the activity of complexes I and II and promotes the formation of complex-I-containing supercomplexes. In vivo, Fat1 is expressed in injured human and mouse arteries, and inactivation of SMC Fat1 in mice potentiates the response to vascular damage, with markedly increased medial hyperplasia and neointimal growth, and evidence of higher SMC mitochondrial respiration. These studies suggest that Fat1 controls mitochondrial activity to restrain cell growth during the reparative, proliferative state induced by vascular injury. Given recent reports linking Fat1 to cancer, abnormal kidney and muscle development, and neuropsychiatric disease8–13, this Fat1 function may have importance in other settings of altered cell growth and metabolism.

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Human NDUFS3 gene coding for the 30-kDa subunit of mitochondrial Complex I: genomic organization and expression

Cited by 12 publications

References 9 publications

Respiratory chain complex I deficiency

Respiratory chain complex I deficiency

Biomarker signatures of mitochondrial NDUFS3 in invasive breast carcinoma

Control of mitochondrial function and cell growth by the atypical cadherin Fat1

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