Affinage

SURF1

Surfeit locus protein 1 · UniProt Q15526

Length
300 aa
Mass
33.3 kDa
Annotated
2026-04-28
89 papers in source corpus 24 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SURF1 is a mitochondrial inner membrane assembly factor essential for biogenesis of cytochrome c oxidase (complex IV), functioning at an early stage to facilitate heme a cofactor insertion into the COX1 catalytic subunit and to promote subsequent incorporation of COX2 into nascent COX1-containing assembly intermediates (PMID:9843204, PMID:14607829, PMID:19625251). Bacterial Surf1 proteins bind heme a with 1:1 stoichiometry and submicromolar affinity through conserved residues in their transmembrane helices, and a conserved tryptophan coordinates the formyl group of heme a to orient it for transfer from heme a synthase to subunit I (PMID:19625251, PMID:21418525). Loss-of-function mutations in SURF1 cause Leigh syndrome, a severe mitochondrial encephalopathy characterized by COX deficiency; in patient fibroblasts, assembly stalls at the COX1·COX4·COX5A subassembly with residual COX sequestered into respiratory supercomplexes (PMID:9843204, PMID:14607829, PMID:22465034). In yeast, the ortholog Shy1 additionally couples Cox1 translational regulation to COX assembly through interactions with the translational regulators Mss51 and Cox14, and participates in respiratory supercomplex formation (PMID:17882259, PMID:20624914).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1994 High

    Before SURF1's mitochondrial function was known, identifying its transcriptional regulation established that YY1 drives SURF1 expression from a bidirectional CpG-island promoter shared with SURF2, linking SURF1 to housekeeping gene regulatory logic.

    Evidence Gel retardation, antibody supershift, and overexpression assays in mammalian cells

    PMID:7731802 PMID:8034020

    Open questions at the time
    • Whether YY1/ETS-mediated transcriptional control is rate-limiting for COX biogenesis in any tissue
    • Physiological signals that modulate SURF1 transcription in vivo
  2. 1997 High

    Identification of the yeast ortholog SHY1 as a mitochondrial inner membrane protein required for COX activity established the first genetic model linking the SURF1 gene family to complex IV biogenesis.

    Evidence Yeast pet mutant complementation, gene disruption, antibody-based localization in S. cerevisiae

    PMID:9162072

    Open questions at the time
    • Molecular mechanism by which Shy1 promotes COX assembly was unresolved
    • Unclear whether the function was conserved in humans
  3. 1998 High

    Demonstration that SURF1 mutations cause COX-deficient Leigh syndrome in humans, with rescue by chromosome transfer, established SURF1 as a bona fide disease gene and confirmed evolutionary conservation of its COX assembly role.

    Evidence Microcell-mediated chromosome transfer complementation and patient mutation sequencing, independently by two laboratories

    PMID:9837813 PMID:9843204

    Open questions at the time
    • Precise step in COX assembly where SURF1 acts was unknown
    • Nature of SURF1's interaction with COX subunits unresolved
  4. 1999 High

    Biochemical characterization showed that mature SURF1 is an integral inner membrane protein with two essential transmembrane domains, and that its loss blocks COX assembly before COX2 incorporation, placing its action at an early assembly step.

    Evidence Alkaline carbonate extraction, mitochondrial import assay, BN-PAGE, deletion mutagenesis with COX activity rescue in patient fibroblasts

    PMID:10556302 PMID:10556303

    Open questions at the time
    • Whether SURF1 directly contacts COX1 or acts on a cofactor was unknown
    • The molecular target of SURF1 at the stalled intermediate was unresolved
  5. 2003 High

    Comparative analysis across patient genotypes pinpointed the assembly block in SURF1-deficient cells to the COX1·COX4·COX5A subassembly stage and revealed that residual assembled COX retains partial electron transfer but loses proton-pumping coupling, defining a functional consequence of incomplete assembly.

    Evidence BN-PAGE immunoblot comparison of SURF1, COX10, and SCO1 patient fibroblasts; spectrophotometric and oxygen consumption assays

    PMID:12943968 PMID:14607829

    Open questions at the time
    • Whether proton-pumping defect reflects altered heme occupancy or subunit composition
    • Structural basis of the incomplete ~90–120 kDa assembly
  6. 2007 High

    In yeast, Shy1 was shown to interact with the Cox1 translational regulators Mss51 and Cox14, establishing that SURF1 orthologs couple translational regulation to assembly and contribute to supercomplex formation, expanding the functional model beyond simple cofactor insertion.

    Evidence Reciprocal co-immunoprecipitation, mass spectrometry, and genetic analysis in S. cerevisiae

    PMID:17882259

    Open questions at the time
    • Whether human SURF1 similarly couples COX1 translation to assembly
    • Structural basis of Shy1–Mss51–Cox14 interaction
  7. 2007 High

    Surf1 knockout mice revealed that SURF1 loss alters neuronal calcium homeostasis and confers neuroprotection against excitotoxicity, suggesting a link between COX deficiency and mitochondrial calcium buffering relevant to Leigh syndrome neuropathology.

    Evidence Constitutive knockout mouse, primary neuronal calcium imaging, kainic acid neurotoxicity model

    PMID:17210671

    Open questions at the time
    • Whether altered Ca²⁺ handling is a direct consequence of reduced COX or an indirect adaptive response
    • Relevance to human Leigh syndrome neurodegeneration not directly tested
  8. 2009 High

    Biochemical reconstitution with bacterial Surf1 proteins demonstrated direct heme a binding with 1:1 stoichiometry and submicromolar affinity, providing the first evidence that Surf1 functions as a heme a delivery factor for COX subunit I.

    Evidence In vivo co-expression with heme a synthesis enzymes, redox difference spectroscopy, isothermal titration calorimetry, site-directed mutagenesis in P. denitrificans

    PMID:18582433 PMID:19625251

    Open questions at the time
    • Whether human SURF1 binds heme a with equivalent affinity
    • The mechanism of heme a transfer from Surf1 to COX1 in the membrane
  9. 2011 High

    Identification of specific transmembrane residues controlling heme a binding and a conserved tryptophan that discriminates heme a from heme o established the molecular determinants of Surf1's heme specificity and oriented the cofactor for transfer to subunit I; concurrently, yeast modeling of Leigh syndrome mutations revealed two distinct failure modes—protein instability (G124E) versus assembly intermediate trapping with loss of Cox1 translational feedback (Y274D).

    Evidence In vitro heme transfer assay with site-directed mutagenesis in bacterial Surf1; yeast pulse-chase stability assays and BN-PAGE with Leigh-equivalent mutations

    PMID:20624914 PMID:21418525 PMID:21470975

    Open questions at the time
    • No structure of a Surf1–heme a complex at atomic resolution
    • How the two distinct failure modes relate to clinical severity in patients
  10. 2012 High

    Detailed analysis of SURF1-deficient patient cells showed that residual COX is exclusively sequestered in I–III₂–IV supercomplexes and that COX5a accumulates as a free subunit, revealing that SURF1 loss reorganizes both COX assembly kinetics and supercomplex distribution.

    Evidence BN-PAGE, 2D gel electrophoresis, Western blot across 9 patient fibroblast lines

    PMID:22465034

    Open questions at the time
    • Whether preferential supercomplex incorporation is a cause or consequence of reduced COX monomer pool
    • Mechanism by which SURF1 loss favors I–III₂–IV over larger supercomplexes
  11. 2016 High

    Cross-species comparison revealed that human cells are more dependent on SURF1 for COX biogenesis than mouse cells, with slower assembly kinetics and more severe intermediate accumulation in humans, explaining the milder phenotype of Surf1 knockout mice relative to human patients.

    Evidence 2D BN-PAGE/SDS-PAGE and pulse-chase metabolic labeling in human patient and mouse knockout fibroblasts

    PMID:26804654

    Open questions at the time
    • Molecular basis of species-specific dependence on SURF1
    • Whether other assembly factors partially compensate in mouse

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of SURF1-mediated heme a transfer to COX1 in the mammalian mitochondrial inner membrane, and whether human SURF1 directly engages Cox1 translational regulation as yeast Shy1 does, remain unresolved.
  • No high-resolution structure of mammalian SURF1 or SURF1–COX1 complex
  • Heme a transfer from SURF1 to COX1 not reconstituted with mammalian proteins
  • Whether SURF1 has roles beyond heme delivery (e.g., copper coordination or COX2 recruitment) in human cells

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 3 GO:0008289 lipid binding 2
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-1643685 Disease 2
Partners
COA2COX10COX14COX4I1COX5AMSS51MT-CO1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 SURF1 encodes a factor required for biogenesis of the cytochrome c oxidase (COX/complex IV) complex; loss-of-function mutations in SURF1 cause COX deficiency in Leigh syndrome patients, and complementation of patient fibroblasts by microcell-mediated chromosome 9q34 transfer rescued the respiratory chain deficiency. Microcell-mediated chromosome transfer complementation, DNA sequencing of patient fibroblasts Nature genetics High 9837813 9843204
1999 Mature SURF1 protein (Surf-1p, ~30 kDa) is imported into mitochondria as a larger precursor (~40 aa N-terminal leader cleaved), is tightly bound to the mitochondrial inner membrane (resistant to alkaline carbonate extraction), and loss of SURF1 blocks COX assembly at an early step, likely before incorporation of subunit II into COX subunit I-containing intermediates. Western blot with anti-HA antibodies, alkaline carbonate extraction, blue native 2D gel electrophoresis, mitochondrial import assay Human molecular genetics High 10556302 10556303
1999 hSurf1 is an integral inner membrane protein; deletion of either transmembrane domain or disruption of the C-terminal transmembrane domain abolishes protein accumulation and fails to rescue COX activity in patient cells, demonstrating that both transmembrane domains in the intact protein are necessary for function. Mitochondrial import assay, proteinase K protection, alkaline carbonate extraction, truncation/deletion mutagenesis with COX activity rescue assay in patient fibroblasts Human molecular genetics High 10556303
1997 SHY1, the yeast (S. cerevisiae) homolog of SURF1, encodes a mitochondrial inner membrane protein required for normal cytochrome c oxidase activity and respiration; deletion of SHY1 produces COX deficiency. Genetic complementation of yeast pet mutants, antibody-based localization, gene disruption The Journal of biological chemistry High 9162072
2003 In SURF1-deficient cells, COX assembly stalls at the MTCO1·COX4·COX5A subassembly stage, implicating SURF1 in promoting the association of MTCO2 with this intermediate; this places SURF1 action after heme A incorporation into MTCO1 but before MTCO2 joining. Immunoblot analysis of native gels (BN-PAGE) on patient fibroblasts with mutations in COX10, SCO1, or SURF1 The Journal of biological chemistry High 14607829
2007 Yeast Shy1 (SURF1 ortholog) promotes complex IV biogenesis by associating with (i) Mss51 and Cox14, translational regulators of Cox1, and (ii) COX assembly subcomplexes; Shy1 thereby links Cox1 translational regulation to complex IV assembly and supercomplex formation. Co-immunoprecipitation, mass spectrometry, genetic analysis, identification of novel assembly factor Coa1 The EMBO journal High 17882259
2009 Bacterial Surf1 proteins (Surf1c and Surf1q from Paracoccus denitrificans) bind heme a in a 1:1 stoichiometry with submicromolar Kd; a conserved histidine residue is critical for heme binding, supporting a direct role for Surf1 in heme a cofactor insertion into COX subunit I. In vivo co-expression with heme a synthesis enzymes, redox difference spectroscopy, isothermal titration calorimetry, site-directed mutagenesis The Journal of biological chemistry High 19625251
2011 In vitro heme a transfer from heme a synthase (CtaA) to Surf1c was demonstrated; mutation of four conserved residues in transmembrane helices of Surf1c/Surf1q abolished heme binding, and mutation of a conserved tryptophan in TM helix II switched heme specificity from heme a to heme o, indicating this residue coordinates the formyl group of heme a and orients it for transfer to subunit I. In vitro interaction assay, site-directed mutagenesis, spectroscopic heme analysis The FEBS journal High 21418525
2003 Absence of Surf1 protein leads to formation of incomplete (~90–120 kDa) COX assemblies that maintain partial electron transport activity in intact cells but have impaired proton pumping (H⁺-pumping), and these incomplete assemblies are destabilized by detergent, indicating Surf1 is required for structural integrity of assembled COX. Spectrophotometric COX assay, oxygen consumption in whole cells, cytofluorometry of mitochondrial membrane potential, immunoelectrophoresis on native gels Biochimica et biophysica acta High 12943968
2008 In P. denitrificans, Surf1c specifically supports aa3-type cytochrome c oxidase assembly and Surf1q supports ba3-type quinol oxidase assembly; heme content analysis of purified COX from surf1 deletion strains indicates Surf1 is involved in early cofactor (heme) insertion into subunit I. Chromosomal gene deletion, oxidase activity assays, heme content analysis of purified oxidase, membrane fractionation Biochimica et biophysica acta High 18582433
2011 In yeast, the SURF1 missense mutation G124E (corresponding to human Leigh G124E) causes rapid turnover of the mature Shy1 protein within mitochondria without affecting import, whereas Y274D (Y344D in yeast) does not affect stability but instead causes accumulation in a ~200 kDa COX assembly intermediate and uncouples Cox1 translational feedback from COX assembly. Yeast missense mutagenesis, pulse-chase protein stability assays, BN-PAGE analysis of assembly intermediates, Cox1 translational regulation assays Human molecular genetics High 21470975
2010 In yeast, the Leigh syndrome G137E Shy1 mutation impairs Cox1 hemylation and reduces mitochondrial copper; a genetic suppressor screen identified Coa2, Cox10, and a novel CX9C-motif IMS protein Coa4 as allele-specific suppressors, placing Shy1 in a pathway with heme and copper insertion factors for COX assembly. Yeast mutagenesis, genetic suppressor screen, mitochondrial copper and heme assays Molecular and cellular biology High 20624914
2012 In SURF1-deficient patient fibroblasts, all assembled COX is sequestered exclusively in I–III₂–IV supercomplexes (not larger supercomplexes), and COX assembly subcomplexes of ~85–140 kDa accumulate; additionally, COX5a subunit accumulates as free subunit, revealing that SURF1 loss reorganizes both COX assembly and supercomplex incorporation. BN-PAGE, 2D gel electrophoresis, whole-genome expression profiling, Western blot in patient fibroblasts Biochimica et biophysica acta High 22465034
2016 Species-specific differences in SURF1 dependence for COX assembly were demonstrated: human SURF1 patient fibroblasts accumulate abundant COX1 assembly intermediates with preferential COX incorporation into I–III₂–IV supercomplexes, whereas SURF1⁻/⁻ mouse fibroblasts show milder intermediate accumulation and more stable COX monomer; pulse-chase metabolic labeling revealed slower COX biogenesis kinetics in human compared to mouse cells. 2D BN-PAGE/SDS-PAGE, pulse-chase metabolic labeling with inhibition of mitochondrial proteosynthesis, immunodetection in mouse and human fibroblasts and tissues Biochimica et biophysica acta High 26804654
2007 Surf1⁻/⁻ knockout mice display a COX assembly defect and show markedly reduced rise of cytosolic and mitochondrial Ca²⁺ in primary neurons and complete protection from kainic acid-induced Ca²⁺-dependent neurotoxicity, indicating that Surf1 loss alters neuronal Ca²⁺ homeostasis independently of its effects on COX assembly. Constitutive knockout mouse, COX activity assay, primary neuronal Ca²⁺ imaging, kainic acid neurotoxicity model Human molecular genetics High 17210671
2014 Surf1⁻/⁻ mice with >50% COX activity reduction show induction of the mitochondrial unfolded protein response (UPRmt) in skeletal muscle and Nrf2 antioxidant pathway in heart as adaptive stress responses, establishing that SURF1 loss-of-function triggers distinct tissue-specific mitochondrial stress signaling. Biochemical assays of ETC complexes, ROS measurement, Western blot for PGC-1α, UPRmt markers (ClpP, Hsp60), Nrf2 pathway in Surf1⁻/⁻ mouse tissues The Biochemical journal High 24911525
1995 The bidirectional Surf-1/Surf-2 promoter is regulated by transcription factor YY1 binding to the Su1 site (stimulating Surf-1 transcription) and by ETS family proteins binding to the Su2 site; CpG methylation of a single cytosine within the ETS consensus site abolishes ETS protein binding and represses promoter activity. Gel retardation assay, methylation interference, in vivo transcription assays with site mutations Nucleic acids research High 7731802
1994 YY1 is identified as the Su1 binding factor of the Surf-1/Surf-2 bidirectional promoter; YY1 overexpression stimulates transcription specifically in the Surf-1 direction. Gel retardation assay, methylation interference, specific antibody supershift, transient transfection overexpression FEBS letters High 8034020
2000 MAP kinase cascade activity and Myc–YY1 interaction are required for serum-stimulated activation of the Surf-1 promoter; Myc overexpression activates Surf-1 transcription through a YY1-binding site, not an E-box, placing MAP kinase and Myc-YY1 upstream of Surf-1 expression. MKP-1 overexpression, Myc-ER fusion activation, promoter mutation analysis in serum-stimulated cells Biochimica et biophysica acta Medium 10858544
2005 Drosophila melanogaster Surf1 (CG9943) knockdown by RNAi causes lethality and COX-selective impairment in adults, while larvae show defects across all respiratory chain complexes and F-ATP synthase; Surf1 silencing in S2R+ cells selectively reduces COX activity and oxygen consumption, confirming Surf1's primary and conserved role in COX assembly. UAS-dsRNA post-transcriptional silencing, COX/respiratory chain enzyme assays, electron microscopy of mitochondria, behavioral/electrophysiological assays Genetics High 16172499
2004 SURF1-deficient patient fibroblasts show elevated P50 for oxygen (2.1–3.3-fold higher than controls) in both intact coupled and digitonin-permeabilized uncoupled cells, demonstrating that SURF1 loss decreases the oxygen affinity of assembled COX. High-resolution respirometry in intact and permeabilized patient fibroblasts American journal of physiology. Cell physiology Medium 15269007
2024 S. pombe Shy1 (SURF1 ortholog) physically interacts with structural subunits and assembly factors of complex IV, and co-immunoprecipitates with Rip1, a complex III subunit, suggesting involvement in respiratory supercomplex assembly; BN-PAGE confirms Shy1 participates in supercomplex formation. Co-immunoprecipitation, BN-PAGE, bioinformatics structural analysis Scientific reports Medium 39289458
2020 A novel SURF1 missense mutation p.P298L significantly compromises COX activity when expressed in COS-7 cells, while not affecting mitochondrial import/localization of the SURF1 protein, indicating this residue is required for SURF1's functional role in COX activity. Transfection of COS-7 cells with mutant SURF1, COX activity assay, mitochondrial localization by fluorescence Mitochondrion Medium 32380162

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature genetics 495 9843204
1998 Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. American journal of human genetics 424 9837813
2007 Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in Surf1 knockout mice. Human molecular genetics 257 17210671
1999 Characterization of SURF-1 expression and Surf-1p function in normal and disease conditions. Human molecular genetics 119 10556302
1997 SHY1, the yeast homolog of the mammalian SURF-1 gene, encodes a mitochondrial protein required for respiration. The Journal of biological chemistry 118 9162072
2003 Cytochrome c oxidase subassemblies in fibroblast cultures from patients carrying mutations in COX10, SCO1, or SURF1. The Journal of biological chemistry 115 14607829
2007 Shy1 couples Cox1 translational regulation to cytochrome c oxidase assembly. The EMBO journal 113 17882259
1999 Expression and functional analysis of SURF1 in Leigh syndrome patients with cytochrome c oxidase deficiency. Human molecular genetics 100 10556303
1999 Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency. Annals of neurology 97 10443880
2014 Complex IV-deficient Surf1(-/-) mice initiate mitochondrial stress responses. The Biochemical journal 92 24911525
2002 MR findings in Leigh syndrome with COX deficiency and SURF-1 mutations. AJNR. American journal of neuroradiology 86 12169463
2005 Tissue-specific cytochrome c oxidase assembly defects due to mutations in SCO2 and SURF1. The Biochemical journal 83 16083427
1995 CpG methylation has differential effects on the binding of YY1 and ETS proteins to the bi-directional promoter of the Surf-1 and Surf-2 genes. Nucleic acids research 83 7731802
2003 Constitutive knockout of Surf1 is associated with high embryonic lethality, mitochondrial disease and cytochrome c oxidase deficiency in mice. Human molecular genetics 75 12566387
2001 Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency. Human mutation 72 11317352
1991 The bidirectional promoter of the divergently transcribed mouse Surf-1 and Surf-2 genes. Molecular and cellular biology 70 1996091
2003 Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR. American journal of neuroradiology 64 12812953
2001 A SURF1 gene mutation presenting as isolated leukodystrophy. Annals of neurology 59 11409433
2000 Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients. Human genetics 55 10746561
2009 Surf1, associated with Leigh syndrome in humans, is a heme-binding protein in bacterial oxidase biogenesis. The Journal of biological chemistry 54 19625251
2013 SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology 51 24027061
2003 Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome. Biochimica et biophysica acta 47 12943968
2012 SURF1-associated Leigh syndrome: a case series and novel mutations. Human mutation 40 22488715
2005 Post-transcriptional silencing and functional characterization of the Drosophila melanogaster homolog of human Surf1. Genetics 39 16172499
2004 Decreased affinity for oxygen of cytochrome-c oxidase in Leigh syndrome caused by SURF1 mutations. American journal of physiology. Cell physiology 38 15269007
1994 The Surf-1 and Surf-2 genes and their essential bidirectional promoter elements are conserved between mouse and human. DNA and cell biology 37 7702754
1999 Sequence conservation from human to prokaryotes of Surf1, a protein involved in cytochrome c oxidase assembly, deficient in Leigh syndrome. FEBS letters 36 10622737
1999 Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency. Human genetics 35 10647889
2010 Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family. Molecular and cellular biology 34 20624914
2000 A novel SURF1 mutation results in Leigh syndrome with peripheral neuropathy caused by cytochrome c oxidase deficiency. Neuromuscular disorders : NMD 34 10899453
2012 Hypertrophic olivary degeneration on magnetic resonance imaging in mitochondrial syndromes associated with POLG and SURF1 mutations. Journal of neurology 33 22729384
2009 SURF1 missense mutations promote a mild Leigh phenotype. Clinical genetics 33 19780766
1994 YY1 is involved in the regulation of the bi-directional promoter of the Surf-1 and Surf-2 genes. FEBS letters 32 8034020
2021 Adeno-associated viral vector serotype 9-based gene replacement therapy for SURF1-related Leigh syndrome. Molecular therapy. Methods & clinical development 29 34703839
2013 Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 29 23838831
2003 SURF1 gene mutations in three cases with Leigh syndrome and cytochrome c oxidase deficiency. Neurology 29 14557577
2012 Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency caused by SURF1 gene mutations. Biochimica et biophysica acta 28 22465034
2011 Role of Surf1 in heme recruitment for bacterial COX biogenesis. Biochimica et biophysica acta 28 21945856
2008 Two variants of the assembly factor Surf1 target specific terminal oxidases in Paracoccus denitrificans. Biochimica et biophysica acta 28 18582433
2007 Light and electron microscopy characteristics of the muscle of patients with SURF1 gene mutations associated with Leigh disease. Journal of clinical pathology 28 17908801
2005 Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations. Journal of child neurology 28 16225813
2018 SURF1 knockout cloned pigs: Early onset of a severe lethal phenotype. Biochimica et biophysica acta. Molecular basis of disease 26 29601977
2004 Novel SURF1 mutation in a child with subacute encephalopathy and without the radiological features of Leigh Syndrome. American journal of medical genetics. Part A 26 15214016
2002 A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. Journal of child neurology 26 12026244
2016 Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts. Redox biology 24 27208630
2001 New splicing-site mutations in the SURF1 gene in Leigh syndrome patients. The Journal of biological chemistry 24 11279059
2016 Tissue- and species-specific differences in cytochrome c oxidase assembly induced by SURF1 defects. Biochimica et biophysica acta 23 26804654
2013 Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations. Brain & development 22 24262866
2014 Leigh syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing. The Journal of biological chemistry 21 25164807
2021 Clinical Diagnosis and Treatment of Leigh Syndrome Based on SURF1: Genotype and Phenotype. Antioxidants (Basel, Switzerland) 20 34943053
2001 Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates. Journal of inherited metabolic disease 20 11804207
2020 SURF1 related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkey. Molecular genetics and metabolism reports 19 33134083
2001 A novel mutation in SURF1 causes skipping of exon 8 in a patient with cytochrome c oxidase-deficient leigh syndrome and hypertrichosis. Molecular genetics and metabolism 19 11509016
2011 Mimicking a SURF1 allele reveals uncoupling of cytochrome c oxidase assembly from translational regulation in yeast. Human molecular genetics 17 21470975
2008 High prevalence of SURF1 c.845_846delCT mutation in Polish Leigh patients. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 17 18583168
2011 Characterization of heme-binding properties of Paracoccus denitrificans Surf1 proteins. The FEBS journal 15 21418525
2012 Two Japanese patients with Leigh syndrome caused by novel SURF1 mutations. Brain & development 14 22410471
2006 Facial dysmorphism in Leigh syndrome with SURF-1 mutation and COX deficiency. Pediatric neurology 14 16765830
2006 Maternal segmental disomy in Leigh syndrome with cytochrome c oxidase deficiency caused by homozygous SURF1 mutation. Neuropediatrics 14 16773507
2018 SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences. Gene 13 29933018
2023 N-acetylcysteine and cysteamine bitartrate prevent azide-induced neuromuscular decompensation by restoring glutathione balance in two novel surf1-/- zebrafish deletion models of Leigh syndrome. Human molecular genetics 12 36795052
2000 Myc and YY1 mediate activation of the Surf-1 promoter in response to serum growth factors. Biochimica et biophysica acta 11 10858544
2018 Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients. Endocrine regulations 10 29715184
2019 Identification of Surf1 as an assembly factor of the cytochrome bc1-aa3 supercomplex of Actinobacteria. Biochimica et biophysica acta. Bioenergetics 9 31226315
2018 Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome. Biochemical and biophysical research communications 8 29481804
2010 Hypoxic and hypercapnic challenges unveil respiratory vulnerability of Surf1 knockout mice, an animal model of Leigh syndrome. Mitochondrion 8 21167962
2009 Heterogeneity of magnetic resonance imaging in Leigh syndrome with SURF1 gene 604G-->C mutation. Clinical imaging 8 19135921
2002 Three novel SURF-1 mutations in Japanese patients with Leigh syndrome. Pediatric neurology 8 11955926
2002 [A new missense mutation of 574C>T in the SURF1 gene--biochemical and molecular genetic study in seven children with Leigh syndrome]. Casopis lekaru ceskych 8 12515039
2023 PKA-Msn2/4-Shy1 cascade controls inhibition of proline utilization under wine fermentation models. Journal of bioscience and bioengineering 6 37940488
2016 Identification of a novel deletion in SURF1 gene: Heterogeneity in Leigh syndrome with COX deficiency. Mitochondrion 6 27756633
2004 Diagnostic difficulties with common SURF1 mutations in patients with cytochrome oxidase-deficient Leigh syndrome. Journal of inherited metabolic disease 6 14970746
2001 SURF1 gene mutations in Polish patients with COX-deficient Leigh syndrome. Journal of applied genetics 6 14564068
2021 Dexmedetomidine Reverses Postoperative Spatial Memory Deficit by Targeting Surf1 and Cytochrome c. Neuroscience 5 33895343
2009 SURF-1 gene mutation associated with leukoencephalopathy in a 2-year-old. Journal of child neurology 5 19805825
2024 Characterization of Shy1, the Schizosaccharomyces pombe homolog of human SURF1. Scientific reports 4 39289458
2024 SURF1 Deficiency: Expanding on Disease Phenotype and Assessing Disease Burden by Describing Clinical and Biochemical Phenotype. American journal of medical genetics. Part A 4 39632678
2010 [Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics]. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova 4 20436434
2005 [Cytochrome c oxydase-deficient Leigh syndrome with homozygous mutation in SURF1 gene]. Archives de pediatrie : organe officiel de la Societe francaise de pediatrie 4 15885549
2025 Improved AAV9-based gene therapy design for SURF1-related Leigh syndrome with minimal toxicity. Molecular therapy. Methods & clinical development 3 40893166
2020 Novel p.P298L SURF1 mutation in thiamine deficient Leigh syndrome patients compromises cytochrome c oxidase activity. Mitochondrion 3 32380162
2004 Pathogenicity of missense mutations in SURF1 deficiency inducing the Leigh syndrome. Importance in diagnosis. Mitochondrion 3 16120373
2021 A colorimetric biosensor for ultrasensitive detection of the SURF1 gene based on a dual DNA-induced cascade hybridization reaction. Analytical methods : advancing methods and applications 2 34569567
2020 Facial Dysmorphism, Hirsutism, and Failure to Thrive as Manifestation of Leigh Syndrome in a Child with SURF1 Mutation. Journal of pediatric neurosciences 1 33042241
2016 Data on cytochrome c oxidase assembly in mice and human fibroblasts or tissues induced by SURF1 defect. Data in brief 1 27408912
1997 Transcripts containing the sea urchin retroposon family 1 (SURF1) in embryos of the sea urchin Anthocidaris crassispina. Zoological science 1 9520637
2026 Study on Leigh syndrome caused by SURF1 gene mutations and its mechanisms. Frontiers in neurology 0 42004432
2024 Distinct Imaging Markers of Leigh's Disease Linked to SURF1 Mutation: A Pediatric Case Study. The American journal of case reports 0 39080924
2020 Functional studies of Plasmodium falciparum putative SURF1 in Saccharomyces cerevisiae. Journal of vector borne diseases 0 34856712