Disease relevance of SURF1

• SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome [1].
• These data suggest a role for SURF1 in the biogenesis of the COX complex and define a new class of gene defects causing human neurodegenerative disease [1].
• This review summarizes recent developments, including our efforts in elucidation of the molecular basis of human mitochondrial diseases due to specific defects of COX with special focus on SURF1 assembly protein [2].
• The aim of the study was to determine whether respiratory alkalosis is characteristic of patients with LS due to SURF1 mutations [3].
• Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates [3].

Psychiatry related information on SURF1

• Given the present rate of producing psychiatrists, shifts in demands for psychiatric services, changing payment and access patterns regarding specialty medical care, increasing numbers of nonpsychiatrist mental health professionals, and a probable surfeit of primary care physicians, underemployment of psychiatrists may become commonplace [4].
• However, it is important to stress that even a calcium surfeit will not prevent or reverse bone loss due to inactivity, gonadal hormone deficiency, alcohol abuse or, indeed, any other factor [5].
• Satiation corresponds to the set point, deviations below which are called hunger or craving, deviations above which are called surfeit [6].
• We found three gender-related features of OCD: males show an earlier age at onset with a lower impact of precipitant events in triggering the disorder; OCD seems to occur in a relative high proportion of males who already have phobias and/or tic disorders; and a surfeit of chronic course of the illness in males in comparison with females [7].
• It appears to be a conglomerate term to encompass chronic anxiety without panic, mild depression without despair, neurasthenia without malaise, a smattering hypochondriasis and a surfeit of illness behavior, all superimposed on passive, dependent individuals with borderline normal intelligence and exposed to profound sociocultural deprivation [8].

High impact information on SURF1

• In this construction the renin system primarily defends sodium balance and blood pressure, with the atrial hormone having an increasing counter-influence in situations involving high blood pressure or sodium surfeit [9].
• I propose that the TFA in partially hydrogenated fats impair lipoprotein receptors during energy surfeit, leading to hypercholesterolaemia, atherogenesis, obesity, and insulin resistance [10].
• A surfeit of RAD51-like genes [11]?
• The brief surfeit of MYC activity was accompanied by evidence of genomic instability, including karyotypic abnormalities, gene amplification, and hypersensitivity to DNA-damaging agents [12].
• Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency [13].

Chemical compound and disease context of SURF1

• SURF1-mutations were identified in three out of four cases with Leigh syndrome while a mutation in the mitochondrial tRNA (trp) gene was identified in the fourth [14].
• In Paracoccus denitrificans, the Surf1 homologue is found in the quinol oxidase operon, suggesting that Surf1 is associated with a primitive quinol oxidase which belongs to the same superfamily as cytochrome oxidase [15].

Biological context of SURF1

• Sequence analysis of SURF1 gene in our three patients revealed seven heterozygous mutations, six of which were new : an insertion, a nonsense mutation, a splicing mutation of intron 7 in addition to three missense mutations [16].
• The human surfeit locus occupies about 60 kb of DNA, and the tightly clustered gene organization and the juxtaposition of the human genes are similar to the mouse and chicken surfeit loci with the 5' end of each gene associated with a CpG-rich island [17].
• This allows us to determine the orientation of the Surfeit and ABO loci with respect to each other and to the telomere and centromere of human chromosome 9 [17].
• A contig of 200 kb containing the human Surfeit locus has been constructed from overlapping cosmid, P1, and PAC clones [17].
• These results indicate important functions for SURF1 specifically related to COX activity and suggest a crucial role of mitochondrial energy pathways in organogenesis and CNS development and function [18].

Anatomical context of SURF1

• We studied fibroblast cultures from patients carrying mutations in the assembly factors COX10, SCO1, or SURF1 [19].
• Surf1p is a protein of the inner membrane of mitochondria that functions in the assembly of cytochrome-c oxidase [20].
• The same analysis revealed that no protein is present in cell lines harboring loss-of-function mutations of SURF-1, regardless of their type and position [21].
• The mitochondrial membrane potential was unchanged in KO versus wild-type neurons, suggesting that the effects of the ablation of Surf1 on Ca(2+) homeostasis, and possibly on longevity, may be independent, at least in part, from those on COX assembly and mitochondrial bioenergetics [22].
• RESULTS: All LS SURF-1 patients had lesions in the brain stem and subthalamic nuclei [23].

Associations of SURF1 with chemical compounds

• Both D7 and C2 contain a common sequence that is 62% homologous to the sea urchin retroposon family 1 (SURF1) [24].
• By using in vitro DNase I, dimethyl sulfate methylation, and gel retardation assays, we have identified five putative promoter control elements between and around the Surf-1 and Surf-2 start sites [25].
• Increased insulin (and leptin as well) locally within the brain complements other signals that indicate a surfeit of energy in the body, including satiety signals generated by the gut during meals, glucose, and some fatty acids [26].
• We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex [27].
• A surfeit of serotonin: sumatriptan and serotonergic antidepressants [28].

Regulatory relationships of SURF1

• A functional YY1 binding site is necessary and sufficient to activate Surf-1 promoter activity in response to serum growth factors [29].

Other interactions of SURF1

• Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1 [30].
• Mutations in the homologous human gene (SURF1) have been reported to cause Leigh's syndrome, a neurological disease associated with COX deficiency [31].
• Human Surf-1 and Surf-2 cDNAs have been cloned and sequenced [32].
• CONCLUSIONS: The clinical and biochemical phenotypes in COX15 defects are more heterogeneous than in other conditions associated with COX deficiency, such as mutations in SURF1 [33].
• All of the patients with mutations in SURF-1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome [34].

Analytical, diagnostic and therapeutic context of SURF1

• Using the human clone as a biotinylated probe for fluorescence in situ hybridization (FISH) we have confirmed the location of the human Surfeit locus to chromosome band 9q34 [35].
• Northern blot analysis showed the virtual absence of specific SURF-1 transcripts in different mutant cell lines [21].
• Finally, experiments based on 2D gel electrophoresis indicated that assembly of COX in SURF-1 null mutants is blocked at an early step, most likely before the incorporation of subunit II in the nascent intermediates composed of subunit I alone or subunit I plus subunit IV [36].
• We have cloned seven Fugu genes which are closely linked to Surfeit genes in two regions of the Fugu genome and have mapped and ordered their human homologues both by PCR analysis of the Genebridge 4 panel of radiation hybrids and by fluorescence in situ hybridization [37].
• Western blot analysis showed that Surf1 protein was absent in all four patients harboring mutations [27].

References