NDUFAF1

Last update 23 Jan 2025

Basic Info

Synonyms

CGI-65, CIA30, Complex I intermediate-associated protein 30, mitochondrial

+ [3]

Introduction

As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.

100 Clinical Results associated with NDUFAF1

100 Translational Medicine associated with NDUFAF1

0 Patents (Medical) associated with NDUFAF1

201

Literatures (Medical) associated with NDUFAF1

01 Nov 2024·Redox Biology

Physioxia rewires mitochondrial complex composition to protect stem cell viability

Article

Author: Gilsbach, Ralf ; Stathopoulou, Konstantina ; Fuchs, Sigrid ; Wrona, Kinga M ; Ulmer, Bärbel M ; Lorenz, Kristina ; Wittig, Ilka ; Zehr, Simonida ; Shibamiya, Aya ; Schulze, Thomas ; Lukowski, Robert ; Wrona, Kinga M. ; Laufer, Sandra D ; Klampe, Birgit ; Ulmer, Bärbel M. ; Hansen, Arne ; Raabe, Janice ; Meisterknecht, Jana ; Laurette, Patrick ; Kaiser, Jennifer ; Cabrera-Orefice, Alfredo ; Brandes, Ralf P. ; Brandes, Ralf P ; Brand, Theresa ; Eschenhagen, Thomas ; Yang, Jiaqi ; Reinsch, Marina ; Thiemann, Ellen ; Cuello, Friederike ; Laufer, Sandra D. ; Orthey, Ellen

Human induced pluripotent stem cells (hiPSCs) are an invaluable tool to study molecular mechanisms on a human background. Culturing stem cells at an oxygen level different from their microenvironmental niche impacts their viability. To understand this mechanistically, dermal skin fibroblasts of 52 probands were reprogrammed into hiPSCs, followed by either hyperoxic (20 % O₂) or physioxic (5 % O₂) culture and proteomic profiling. Analysis of chromosomal stability by Giemsa-banding revealed that physioxic -cultured hiPSC clones exhibited less pathological karyotypes than hyperoxic (e.g. 6 % vs. 32 % mosaicism), higher pluripotency as evidenced by higher Stage-Specific Embryonic Antigen 3 positivity, higher glucose consumption and lactate production. Global proteomic analysis demonstrated lower abundance of several subunits of NADH:ubiquinone oxidoreductase (complex I) and an underrepresentation of pathways linked to oxidative phosphorylation and cellular senescence. Accordingly, release of the pro-senescent factor IGFBP3 and β-galactosidase staining were lower in physioxic hiPSCs. RNA- and ATAC-seq profiling revealed a distinct hypoxic transcription factor-binding footprint, amongst others higher expression of the HIF1α-regulated target NDUFA4L2 along with increased chromatin accessibility of the NDUFA4L2 gene locus. While mitochondrial DNA content did not differ between groups, physioxic hiPSCs revealed lower polarized mitochondrial membrane potential, altered mitochondrial network appearance and reduced basal respiration and electron transfer capacity. Blue-native polyacrylamide gel electrophoresis coupled to mass spectrometry of the mitochondrial complexes detected higher abundance of NDUFA4L2 and ATP5IF1 and loss of incorporation into complex IV or V, respectively. Taken together, physioxic culture of hiPSCs improved chromosomal stability, which was associated with downregulation of oxidative phosphorylation and senescence and extensive re-wiring of mitochondrial complex composition.

01 Nov 2024·Biochimica et Biophysica Acta (BBA) - Bioenergetics

Structural robustness of the NADH binding site in NADH:ubiquinone oxidoreductase (complex I)

Article

Author: Wohlwend, Daniel ; Friedrich, Thorsten ; Göppert-Asadollahpour, Sanaz

Energy converting NADH:ubiquinone oxidoreductase, complex I, is the first enzyme of respiratory chains in most eukaryotes and many bacteria. Mutations in genes encoding subunits of human complex I may lead to its dysfunction resulting in a diverse clinical pattern. The effect of mutations on the protein structure is not known. Here, we focus on mutations R88G, E246K, P252R and E377K that are found in subunit NDUFV1 comprising the NADH binding site of complex I. Homologous mutations were introduced into subunit NuoF of Aquifex aeolicus complex I and it was attempted to crystallize variants of the electron input module, NuoEF, with bound substrates in the oxidized and reduced state. The E377K variant did not form crystals most likely due to an improper protein assembly. The architecture of the NADH binding site is hardly affected by the other mutations indicating its unexpected structural robustness. The R88G, E246K and P252R mutations led to small local structural rearrangements that might be related to their pathogenicity. These minor structural changes involve substrate binding, product release and the putative formation of reactive oxygen species. The structural consequences of the mutations as obtained with the bacterial enzyme might thus help to contribute to the understanding of disease causing mutations.

01 Apr 2024·Plant Science

PuNDH9, a subunit of ETC Complex I regulates plant defense by interacting with PuPR1

Article

Author: Qiao, Qinghai ; Han, Chenyang ; Zhao, Keke ; Su, Zhiyuan ; Wang, Xin ; Qi, Kaijie ; Zhang, Shaoling ; Huang, Xiaosan ; Xie, Zhihua

NAD⁺ and NADH play critical roles in energy metabolism, cell death, and gene expression. The NADH-ubiquinone oxidoreductase complex (Complex I) has been long known as a key enzyme in NAD⁺ and NADH metabolism. In the present study, we found and analyzed a new subunit of Complex I (NDH9), which was isolated from Pyrus ussuriensis combined with RT-PCR. Following infection with A. alternata, RT-qPCR analysis demonstrated an increase in the expression of PuNDH9. Genetic manipulation of PuNDH9 levels suggested that PuNDH9 plays key roles in NADH/NAD⁺ homeostasis, defense enzyme activities, ROS generation, cell death, gene expression, energy metabolism, and mitochondrial functions during the pear- A. alternata interaction. Furthermore, Y2H, GST-pull down, and a split-luciferase complementation imaging assays revealed that PuNDH9 interacts with PuPR1. We discover that PuNDH9 and PuPR1 synergistically activate defense enzyme activities, ROS accumulation, cell death, and plant defenses. Collectively, our findings reveal that PuNDH9 is likely important for plant defenses.

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NDUFAF1

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