Mutations of the SCO1 Gene in Mitochondrial Cytochrome c Oxidase Deficiency with Neonatal-Onset Hepatic Failure and Encephalopathy

Valnot, Isabelle; Osmond, Sandrine; Gigarel, Nadine; Mehaye, Blandine; Amiel, Jeanne; Cormier‐Daire, Valérie; Münnich, Arnold; Bonnefont, Jean‐Paul; Rustin, Pierre; Rötig, Agnès

doi:10.1016/s0002-9297(07)62940-1

Cited by 207 publications

(203 citation statements)

References 32 publications

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“…Exceptions can be applied for instance to complex III-deficient patients harbouring mutations in the assembly factors BCS1L and TTC19, who showed normal complex I activity levels despite of a dramatic loss of fully-assembled complex III in different tissues (Fernandez-Vizarra et al, 2007;Ghezzi et al, 2011). Similarly, mutations in complex IV subunits or assembly factors often lead to isolated complex IV defects without complex I being affected (Tiranti et al, 1998;Zhu et al, 1998;Papadopoulou et al, 1999;Rahman et al, 1999;Valnot et al, 2000a;Valnot et al, 2000b;Antonicka et al, 2003;Massa et al, 2008). Such differences might be attributed to the nature of the mutation or the functional role of the OXPHOS mutated gene, and suggest that not all complexes III and IV structural genes are equally necessary to maintain complex I stability.…”

Section: Respiratory Chain Dysfunction: a Coupling Of Defective Assemmentioning

confidence: 99%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

140

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For decades mitochondria have been considered static round shaped organelles in charge of energy production. On the contrary, they are highly dynamic cellular components that undergo continuous cycles of fusion and fission influenced, for instance, by oxidative stress, cellular energy requirements, or the cell cycle state. New important functions beyond energy production have been attributed to mitochondria, such as the regulation of cell survival due to their role in the modulation of apoptosis, autophagy and aging. Primary mitochondrial diseases due to mutations in genes involved in these new mitochondrial functions, and the implication of mitochondrial dysfunction in multifactorial human pathologies like cancer, Alzheimer's and Parkinson's diseases, or diabetes has been demonstrated. Therefore, mitochondria are set at a central point of the equilibrium between health and disease, and a better understanding of mitochondrial functions will open new fields to explore the role of these mitochondrial pathways in human pathologies. The present review will dissect the relationships between the activity and assembly defects of the mitochondrial respiratory chain, oxidative damage, and alterations in mitochondrial dynamics, with special focus at their implications in neurodegeneration.

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Section: Respiratory Chain Dysfunction: a Coupling Of Defective Assemmentioning

confidence: 99%

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Morán

Moreno-Lastres

Marín-Buera

et al. 2012

Free Radical Biology and Medicine

140

View full text Add to dashboard Cite

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“…Both encode mt proteins (Petruzzella et al, 1998;Paret et al, 1999), which are essential for mt function as shown by the recent detection of mutations associated with fatal COX deficiencies. Mutations in hSCO2 were reported in infants who suffered from a fatal disorder with hypertrophic cardiomyopathy as the predominant symptom (Papadopoulou et al, 1999;Jaksch et al, 2000Jaksch et al, , 2001a whereas the key symptoms of the infant patients carrying mutations in the hSCO1 gene were hepatic failure and ketoacidotic coma (Valnot et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of Saccharomyces cerevisiae Sco2p reveals a high degree of redundancy with Sco1p

Lode¹,

Paret²,

Rödel³

2002

Yeast

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The Saccharomyces cerevisiae gene SCO1 has been shown to play an essential role in the transfer of copper to the Cu A -centre of the mitochondrial cytochrome c oxidase subunit Cox2p. By contrast, the function of Sco2p, the gene product of the highly homologous SCO2 gene, remains to be elucidated. Deletion of the SCO2 gene does not affect growth on a variety of carbon sources, including glycerol, lactate and ethanol. We report here, that Sco2p is anchored in the mitochondrial membrane by a single transmembrane segment and displays a similar tripartite structure as Sco1p. Most parts of Sco1p can be replaced by the homologous parts of Sco2p without loss of function. A short stretch of 13 amino acids, immediately adjacent to the transmembrane region, is crucial for Sco1p function and cannot be replaced by its Sco2p counterpart. We propose that this region is relevant for the correct spatial orientation of the C-terminal part of the protein. Immunoprecipitation and in vitro binding assays show that Sco2p interacts with the C-terminal portion of Cox2p. This interaction is neither dependent on bound copper ions nor on the presence of Sco1p. Furthermore we report on in vitro binding assays which show that Sco2p can form homomeric complexes, but also heteromeric complexes with Sco1p. Our data suggest that Sco2p is involved in the transfer of copper to Cox2p, but that this activity is insufficient for oxidative growth and not able to substitute for Sco1p activity.

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“…In addition to mutations in mitochondrial DNA-encoded COX genes 5,6 , mutations in nuclear DNA-encoded COX component genes and COX accessory factors cause COX deficiency [6][7][8] . For example, SURF1 is responsible for Leigh syndrome 9,10 , SCO1 for neonatal-onset hepatic failure and encephalopathy 11 , SCO2 for fatal infantile cardioencephalomyopathy 12 , and COX15 for fatal hypertrophic cardiomyopathy 13 . SCO1 and SCO2 are copper metallochaperones that are necessary for copper insertion into the catalytic core of COX assembly 14 .…”

mentioning

confidence: 99%

A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle

et al. 2013

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The mitochondrial respiratory chain is essential for oxidative phosphorylation and comprises multiple complexes, including cytochrome c oxidase, assembled in macromolecular supercomplexes. Little is known about factors that contribute to supercomplex organization. Here we identify COX7RP as a factor that promotes supercomplex assembly. Cox7rp-knockout mice exhibit decreased muscular activity and heat production failure in the cold due to reduced COX activity. In contrast, COX7RP-transgenic mice exhibit increased exercise performance with increased cytochrome c oxidase activity. Two-dimensional blue native electrophoresis reveals that COX7RP is a key molecule that promotes assembly of the III 2 /IV n supercomplex with complex I. Our study identified COX7RP as a protein that functions in I/III 2 /IV n supercomplex assembly and is required for full activity of mitochondrial respiration.

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Mutations of the SCO1 Gene in Mitochondrial Cytochrome c Oxidase Deficiency with Neonatal-Onset Hepatic Failure and Encephalopathy

Cited by 207 publications

References 32 publications

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

Molecular characterization of Saccharomyces cerevisiae Sco2p reveals a high degree of redundancy with Sco1p

A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle

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