Ndufb1 (MNLL) is one of the smallest accessory subunits of mitochondrial NADH:ubiquinone oxidoreductase (Complex I), a 45-subunit enzyme of the inner mitochondrial membrane that transfers electrons from NADH to ubiquinone and couples this to proton translocation. The 57-amino-acid protein contains a single transmembrane helix that anchors it in the membrane arm near the core subunit ND4, with a short C-terminal domain exposed to the mitochondrial matrix. As a non-catalytic accessory subunit, Ndufb1 contributes to the structural integrity of Complex I and is incorporated during the ND4-module stage of the modular assembly pathway. Cryo-EM structures from mouse heart mitochondria confirm its position in the membrane domain, where it contacts neighboring beta-subcomplex subunits NDUFB4, NDUFB5, NDUFB8, and NDUFB11.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0045271 respiratory chain complex I | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that Ndufb1 is part of respiratory chain complex I. Consistent with all structural and biochemical evidence showing NDUFB1 as an integral subunit of Complex I across eukaryotes. Falcon deep research corroborates membership in the membrane-arm distal P-module (ND4 module) of Complex I. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md NDUFB1 is consistently placed in the **membrane-arm distal P-module**, specifically the **ND4 module** |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Automated annotation placing Ndufb1 in the mitochondrion. Correct but less specific than the mitochondrial inner membrane annotation which is also present. Subsumed by the more specific localization. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome' |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Automated annotation for mitochondrial inner membrane localization. Correct and supported by direct structural evidence from cryo-EM of mouse Complex I showing NDUFB1 embedded in the inner membrane with a single transmembrane helix. Falcon deep research independently places NDUFB1 at the inner mitochondrial membrane via its membrane-arm ND4-module membership. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md NDUFB1 functions at the **inner mitochondrial membrane** as part of complex I |
| GO:0045271 respiratory chain complex I | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara-based transfer from human ortholog. Correct and redundant with the IBA and IDA annotations for the same term. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0005739 mitochondrion | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: Manual transfer from human ortholog O75438. Correct but less specific than the inner membrane annotation. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome' |
| GO:0005743 mitochondrial inner membrane | ISO GO_REF:0000119 | ACCEPT | Summary: Manual transfer from human ortholog O75438 for mitochondrial inner membrane localization. Correct, and confirmed directly in mouse by cryo-EM (PMID:38575788). Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0045271 respiratory chain complex I | ISO GO_REF:0000119 | ACCEPT | Summary: Manual transfer from human ortholog. Correct and redundant with IDA and IBA annotations for the same term. Supporting Evidence: PMID:38575788 Supercomplexes of the respiratory chain...mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0016607 nuclear speck | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: Transfer from human ortholog O75438 for nuclear speck localization. This is a questionable annotation for a well-characterized mitochondrial inner membrane protein. NDUFB1 is a single-pass transmembrane protein that is an integral part of the membrane arm of Complex I. No published study has demonstrated dual mitochondrial/nuclear localization for this protein. The human annotation may derive from a high-throughput study with false-positive nuclear detections, possibly due to the very small size of the protein (57 aa) leading to mislocalization artifacts. Reason: No credible evidence supports nuclear speck localization for a small transmembrane Complex I subunit. Likely a false positive from high-throughput localization screening. |
| GO:0009060 aerobic respiration | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | KEEP AS NON CORE | Summary: ComplexPortal annotation based on the review by Signes and Fernandez-Vizarra 2018. As a structural subunit of Complex I, NDUFB1 participates in the respiratory chain and therefore in aerobic respiration. The term is correct but broad; the more specific process is mitochondrial electron transport from NADH to ubiquinone. Supporting Evidence: PMID:30030361 The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process |
| GO:0042776 proton motive force-driven mitochondrial ATP synthesis | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | KEEP AS NON CORE | Summary: ComplexPortal annotation. Complex I contributes to the proton motive force by pumping protons across the inner membrane, which drives ATP synthase. NDUFB1 as a structural subunit contributes indirectly to this process. However, NDUFB1 itself is not in the proton-pumping modules directly; it is a structural element. The annotation is not wrong but represents an indirect contribution. Supporting Evidence: PMID:30030361 The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process |
| GO:0005743 mitochondrial inner membrane | IDA PMID:38575788 SCAF1 drives the compositional diversity of mammalian respir... | ACCEPT | Summary: Direct experimental evidence from cryo-EM of mouse heart mitochondria showing NDUFB1 as part of Complex I in the inner membrane. The is_active_in qualifier is appropriate since this is where the protein functions as part of the respirasome. Supporting Evidence: PMID:38575788 mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0045271 respiratory chain complex I | IDA PMID:38575788 SCAF1 drives the compositional diversity of mammalian respir... | ACCEPT | Summary: Direct experimental evidence from cryo-EM structures of mouse respirasomes. Ndufb1 is resolved as chain f in the Complex I structure. This is the strongest evidence for this annotation. Supporting Evidence: PMID:38575788 mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0045271 respiratory chain complex I | ISS GO_REF:0000024 | ACCEPT | Summary: Manual sequence similarity-based transfer. Correct and consistent with direct experimental evidence from mouse cryo-EM studies. Supporting Evidence: PMID:38575788 mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV |
| GO:0005198 structural molecule activity | ISS | NEW | Summary: NDUFB1 is a non-catalytic accessory subunit of Complex I. It lacks any catalytic motifs and its role is structural: stabilizing the membrane arm of Complex I around the ND4 core subunit. Structural molecule activity is the appropriate molecular function for accessory subunits that contribute to complex integrity without independent enzymatic activity. Reason: No molecular function annotation currently exists for Ndufb1. As a non-catalytic accessory subunit, structural molecule activity is the most appropriate MF term. Supporting Evidence: PMID:38575788 mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV PMID:27626371 Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans file:mouse/Ndufb1/Ndufb1-deep-research-bioreason-sft.md A small, non-catalytic accessory subunit tailored to the membrane arm of respiratory complex I...This architecture causes the protein to function as a structural and organizational element rather than as an active redox catalyst file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md **NDUFB1 (Ndufb1 in mouse)** is an **accessory (non-catalytic) structural subunit** rather than a redox cofactor–bearing catalytic subunit. |
| GO:0032981 mitochondrial respiratory chain complex I assembly | ISS | NEW | Summary: NDUFB1 is incorporated during the ND4-module stage of Complex I assembly. Systematic studies of accessory subunits in human cells (PMID:27626371) demonstrate that loss of accessory subunits disrupts Complex I assembly. NDUFB1 is part of the ND4-module assembly intermediate along with NDUFB4, NDUFB5, NDUFB6, NDUFB10, NDUFB11. Reason: No Complex I assembly annotation is present despite evidence that NDUFB1 is part of a defined assembly intermediate (ND4-module). Supporting Evidence: PMID:27626371 Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans PMID:30030361 The human enzymes comprise core proteins, performing the catalytic activities, and a large number of 'supernumerary' subunits that play essential roles in assembly, regulation and stability file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md the **ND4 module** (explicitly including **NDUFB1**) was **detected as an assembly intermediate** with an apparent size of approximately **~260 kDa** file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md a subcomplex containing **NDUFB5, NDUFB6, NDUFB10, NDUFB11** is described as assembling early, followed by the addition of **NDUFB1** and **ND4** |
| GO:0006120 mitochondrial electron transport, NADH to ubiquinone | NAS PMID:30030361 Assembly of mammalian oxidative phosphorylation complexes I-... | NEW | Summary: As a structural subunit of Complex I, NDUFB1 is essential for the complex-level activity of NADH to ubiquinone electron transfer. Although NDUFB1 itself is non-catalytic, loss of accessory subunits abolishes Complex I activity. This is more specific than the existing aerobic respiration annotation. Reason: This process term more precisely describes the role of Complex I in mitochondrial electron transport than the broader aerobic respiration term already present. Supporting Evidence: PMID:30030361 The assembly of the five oxidative phosphorylation system (OXPHOS) complexes in the inner mitochondrial membrane is an intricate process PMID:38575788 mammalian (mouse) tissues contain three defined types of 'respirasome', supercomplexes made of CI, CIII2 and CIV file:mouse/Ndufb1/Ndufb1-deep-research-falcon.md It transfers electrons from **NADH to ubiquinone (CoQ)** and couples this redox reaction to **proton translocation across the inner mitochondrial membrane (IMM)** |
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Download this section (compressed HTML)Q: What is the specific phenotype of Ndufb1 knockout in mouse cells or tissues? Does loss of NDUFB1 lead to complete loss of Complex I, or is a partially assembled complex retained?
Suggested experts: Stroud DA
Q: Does NDUFB1 have any role in stabilizing respiratory supercomplexes (respirasomes) beyond its role within Complex I itself?
Suggested experts: Sazanov LA, Vercellino I
Experiment: CRISPR knockout of Ndufb1 in mouse cell lines followed by complexome profiling to determine whether loss of NDUFB1 specifically disrupts the ND4-module assembly intermediate or affects broader Complex I stability.
Type: complexome profiling
Experiment: Crosslinking mass spectrometry of purified mouse Complex I to map the direct protein-protein contacts of NDUFB1 and determine whether it bridges the ND4-module to adjacent assembly modules.
Type: XL-MS
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