NDUFA2 Polyclonal Antibody

PRODUCT DATA SHEET Bioworld Technology,Inc. NDUFA2 polyclonal antibody Catalog: BS71095 Host: Rabbit Reactivity: Human,Mouse BackGround: The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial mem- brane, and may be involved in regulating complex I activ- ity or its assembly via assistance in redox processes. Mu- tations in this gene are associated with Leigh syndrome, Western blot analysis of extract of various cells, using NDUFA2 anti- an early-onset progressive neurodegenerative disorder. body. Alternative splicing results in multiple transcript variants. Product: Rabbit IgG, 1mg/ml in PBS with 0.02% sodium azide, 50% glycerol, pH7.2 Molecular Weight: ~ 11 kDa Swiss-Prot: Immunohistochemistry of paraffin-embedded human esophagus using O43678 NDUFA2 antibody at dilution of 1:100 (x40 lens). Purification&Purity: The antibody was affinity-purified from rabbit antiserum by affinity-chromatography using epitope-specific im- munogen and the purity is > 95% (by SDS-PAGE). Applications: WB 1:500 - 1:2000 IHC 1:50 - 1:200 Storage&Stability: Immunohistochemistry of paraffin-embedded human liver cancer using Store at 4°C short term. Aliquot and store at -20°C long NDUFA2 antibody at dilution of 1:100 (x40 lens). term. Avoid freeze-thaw cycles. Note: Specificity: For research use only, not for use in diagnostic procedure. NDUFA2 polyclonal antibody detects endogenous levels of NDUFA2 protein. DATA: Bioworld Technology, Inc. Bioworld technology, co. Ltd. Add： 1660 South Highway 100, Suite 500 St. Louis Park, Add： No 9, weidi road Qixia District Nanjing, 210046, MN 55416,USA. P. R. China. Email: [email protected] Email: [email protected] Tel: 6123263284 Tel: 0086-025-68037686 Fax: 6122933841 Fax: 0086-025-68035151 .

Copy Link

Recommended publications

Analysis of Translating Mitoribosome Reveals Functional Characteristics of Translation in Mitochondria of Fungi
ARTICLE https://doi.org/10.1038/s41467-020-18830-w OPEN Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi Yuzuru Itoh 1,2,4, Andreas Naschberger1,4, Narges Mortezaei1,4, Johannes M. Herrmann 3 & ✉ Alexey Amunts 1,2 1234567890():,; Mitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly inter- mediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF1) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation. 1 Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 17165 Solna, Sweden. 2 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17165 Solna, Sweden. 3 Cell Biology, University
[Show full text]
NDUFA2 Rabbit Pab
Leader in Biomolecular Solutions for Life Science NDUFA2 Rabbit pAb Catalog No.: A8136 Basic Information Background Catalog No. The encoded protein is a subunit of the hydrophobic protein fraction of the A8136 NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in Observed MW regulating complex I activity or its assembly via assistance in redox processes. Mutations 11kDa in this gene are associated with Leigh syndrome, an early-onset progressive neurodegenerative disorder. Alternative splicing results in multiple transcript variants. Calculated MW 8kDa/10kDa Category Primary antibody Applications WB,IHC,IF Cross-Reactivity Human, Mouse, Rat Recommended Dilutions Immunogen Information WB 1:500 - 1:2000 Gene ID Swiss Prot 4695 O43678 IHC 1:50 - 1:100 Immunogen 1:50 - 1:200 IF Recombinant fusion protein containing a sequence corresponding to amino acids 1-95 of human NDUFA2 (NP_002479.1). Synonyms NDUFA2;B8;CD14;CIB8 Contact Product Information 400-999-6126 Source Isotype Purification Rabbit IgG Affinity purification [email protected] www.abclonal.com.cn Storage Store at -20℃. Avoid freeze / thaw cycles. Buffer: PBS with 0.02% sodium azide,50% glycerol,pH7.3. Validation Data Western blot analysis of extracts of various cell lines, using NDUFA2 antibody (A8136) at 1:1000 dilution. Secondary antibody: HRP Goat Anti-Rabbit IgG (H+L) (AS014) at 1:10000 dilution. Lysates/proteins: 25ug per lane. Blocking buffer: 3% nonfat dry milk in TBST. Detection: ECL Basic Kit (RM00020). Exposure time: 30s. Immunohistochemistry of paraffin- Immunohistochemistry of paraffin- Immunofluorescence analysis of NIH/3T3 embedded human esophagus using embedded human liver cancer using cells using NDUFA2 antibody (A8136) at NDUFA2 antibody (A8136) at dilution of NDUFA2 antibody (A8136) at dilution of dilution of 1:100.
[Show full text]
SI Materials and Methods Materials and Chemicals the DEP and PM Used in This Work Are the Standard Reference Material 2975 and S
SI Materials and Methods Materials and chemicals The DEP and PM used in this work are the Standard Reference Material 2975 and Standard Reference Material 1648a, respectively, from the National Institute of Standards and Technology (NIST, USA). 1-nitropyrene, 1-nitrofluoranthene (BCR305), naphthalene (91489), fluoranthene (F807) and phenanthrene (P11409) were purchased from Sigma-Aldrich Co. LLC (USA). 6-hydroxynitropyrene (6-OHNP) and 8- hydroxynitropyrene (8-OHNP) were synthesized as previously described (1). Subject characterization We recruited 600 healthy volunteers from 3 cities with discrepant outdoor air pollution levels, including 100 male (mean age 65 years, range: 57-72 years) and 100 female (mean age 66 years, range: 56-72 years) in Zhangjiakou; 100 male (mean age 64 years, range: 57-71 years) and 100 female (mean age 64 years, range: 55-72 years) in Nanjing; as well as 100 male (mean age 66 years, range: from 60-73 years) and 100 female (mean age 64, range: 58-73) in Shijiazhuang. All volunteers were healthy non-smokers, free of any diagnosis of respiratory diseases, and lived in urban communities. Blood and mid-stream urine samples were collected between Dec.10th to Dec. 20th, 2014. For the panel study, we recruited 30 male (mean age 64 years, range: 58-71 years) and 30 female (mean age 65 years, range: 57-73 years) retired COPD patients in Nanjing; 30 male (mean age 65 years, range: 59-72 years) and 30 female (mean age 64 years, range: 57-71 years) retired COPD patients in Shijiazhuang. All subjects were living in urban communities and had been diagnosed with mild-to-moderate COPD in Nanjing Chest Hospital or the Second Hospital of Hebei Medical University according to the classification of Global Initiative for Chronic Obstructive Lung Disease (GOLD).
[Show full text]
WO 2017/070647 Al 27 April 2017 (27.04.2017) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/070647 Al 27 April 2017 (27.04.2017) P O P C T (51) International Patent Classification: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, A61K 31/455 (2006.01) C12N 15/86 (2006.01) KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, A61K 31/465 (2006.01) A61P 27/02 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, A61K 31/19 (2006.01) A61P 27/06 (2006.01) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, A61K 48/00 (2006.01) A61K 45/06 (2006.01) SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (21) International Application Number: ZW. PCT/US2016/058388 (84) Designated States (unless otherwise indicated, for every (22) International Filing Date: kind of regional protection available): ARIPO (BW, GH, 24 October 2016 (24.10.201 6) GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (25) Filing Language: English TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (26) Publication Language: English DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, (30) Priority Data: LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, 62/245,467 23 October 2015 (23.
[Show full text]
Electron Transport Chain Activity Is a Predictor and Target for Venetoclax Sensitivity in Multiple Myeloma
ARTICLE https://doi.org/10.1038/s41467-020-15051-z OPEN Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma Richa Bajpai1,7, Aditi Sharma 1,7, Abhinav Achreja2,3, Claudia L. Edgar1, Changyong Wei1, Arusha A. Siddiqa1, Vikas A. Gupta1, Shannon M. Matulis1, Samuel K. McBrayer 4, Anjali Mittal3,5, Manali Rupji 6, Benjamin G. Barwick 1, Sagar Lonial1, Ajay K. Nooka 1, Lawrence H. Boise 1, Deepak Nagrath2,3,5 & ✉ Mala Shanmugam 1 1234567890():,; The BCL-2 antagonist venetoclax is highly effective in multiple myeloma (MM) patients exhibiting the 11;14 translocation, the mechanistic basis of which is unknown. In evaluating cellular energetics and metabolism of t(11;14) and non-t(11;14) MM, we determine that venetoclax-sensitive myeloma has reduced mitochondrial respiration. Consistent with this, low electron transport chain (ETC) Complex I and Complex II activities correlate with venetoclax sensitivity. Inhibition of Complex I, using IACS-010759, an orally bioavailable Complex I inhibitor in clinical trials, as well as succinate ubiquinone reductase (SQR) activity of Complex II, using thenoyltriﬂuoroacetone (TTFA) or introduction of SDHC R72C mutant, independently sensitize resistant MM to venetoclax. We demonstrate that ETC inhibition increases BCL-2 dependence and the ‘primed’ state via the ATF4-BIM/NOXA axis. Further, SQR activity correlates with venetoclax sensitivity in patient samples irrespective of t(11;14) status. Use of SQR activity in a functional-biomarker informed manner may better select for MM patients responsive to venetoclax therapy. 1 Department of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA, USA.
[Show full text]
Taurine Ameliorates Particulate Matter-Induced Emphysema by Switching on Mitochondrial NADH Dehydrogenase Genes
Taurine ameliorates particulate matter-induced PNAS PLUS emphysema by switching on mitochondrial NADH dehydrogenase genes Xiaobo Lia,1, Hongbao Yangb,1, Hao Suna, Runze Lua, Chengcheng Zhanga, Na Gaoa, Qingtao Menga, Shenshen Wua, Susanna Wangc, Michael Aschnerd, Jiong Wue, Boping Tangf, Aihua Gug, Steve A. Kayc,2, and Rui Chena,h,2 aKey Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; bCenter for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China; cDepartment of Neurology, University of Southern California, Los Angeles, CA 90089; dDepartment of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461; eDepartment of Life Science, Zhejiang Technology University, Hangzhou 310018, China; fJiangsu Key Laboratory for Bioresources of Saline Soils, Jiangsu Synthetic Innovation Center for Coastal Bioagriculture, Yancheng Teachers University, Yancheng 224002, China; gState Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China; and hInstitute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China Contributed by Steve A. Kay, September 26, 2017 (sent for review July 13, 2017; reviewed by Mien-Chie Hung and Wang Min) Chronic obstructive pulmonary disease (COPD) has been linked to enhanced oxidative stress are capable of triggering an essential particulate matter (PM) exposure. Using transcriptomic analysis, degradation process known as autophagy (12). we demonstrate that diesel exhaust particles, one of the major The role of autophagy in pulmonary disorders can be either sources of particulate emission, down-regulated genes located in deleterious or protective, depending on the stimuli (13). In cig- mitochondrial complexes I and V and induced experimental COPD in arette-smoke–induced COPD, autophagy is critical in mediating a mouse model.
[Show full text]
Recessive Mutations in NDUFA2 Cause Mitochondrial Leukoencephalopathy
Perrier Stefanie (Orcid ID: 0000-0002-6881-7573) Recessive Mutations in NDUFA2 Cause Mitochondrial Leukoencephalopathy (Short Report) Stefanie Perrier1†, Laurence Gauquelin1,2†, Martine Tétreault3,4, Luan Tran1,2,5,6, Neil Webb3,7,8, Myriam Srour1,2,6, John J. Mitchell2,5, Catherine Brunel-Guitton7, Jacek Majewski3,4, Valynne Long9, Stephanie Keller10, Michael J. Gambello9, Cas Simons11, Care4Rare Canada Consortium, Adeline Vanderver12,13, and Geneviève Bernard1,2,5,6* 1 Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada. 2 Department of Pediatrics, McGill University, Montreal, QC, Canada. 3 Department of Human Genetics, McGill University, Montreal, QC, Canada. 4 McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada. 5 Department of Medical Genetics, Montreal Children’s Hospital, McGill University Health Center, Montreal, QC, Canada. 6 Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. 7 Division of Medical Genetics, Department of Pediatrics, CHU Sainte-Justine and Université de Montréal, Montreal, QC, Canada. 8 Montreal Neurological Institute, McGill University, Montreal, QC, Canada. 9 Department of Human Genetics, Division of Medical Genetics, Emory University School of Medicine, Atlanta, GA, USA. 10 Department of Pediatrics, Division of Pediatric Neurology, Emory University School of Medicine, Atlanta, GA, USA. 11 Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Queensland, Australia. 12 Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 13 Division of Neurology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA. † Both authors contributed equally. *Correspondence to: Dr. Geneviève Bernard Research Institute of the McGill University Health Centre 1001 boul Décarie EM02224 (CHHD Mail Drop Point #EM03211 (Cubicle C)) Montréal, QC H4A3J1, Canada.
[Show full text]
Instability in NAD Metabolism Leads to Impaired Cardiac Mitochondrial
RESEARCH ARTICLE Instability in NAD+ metabolism leads to impaired cardiac mitochondrial function and communication Knut H Lauritzen1*, Maria Belland Olsen1, Mohammed Shakil Ahmed2, Kuan Yang1, Johanne Egge Rinholm3, Linda H Bergersen4,5, Qin Ying Esbensen6, Lars Jansen Sverkeli7, Mathias Ziegler7, Ha˚ vard Attramadal2, Bente Halvorsen1,8, Pa˚ l Aukrust1,8,9, Arne Yndestad1,8 1Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet and University of Oslo, Oslo, Norway; 2Institute for Surgical Research, Oslo University Hospital and University of Oslo, Oslo, Norway; 3Department of Microbiology, Oslo University Hospital, Oslo, Norway; 4Department of Oral Biology, University of Oslo, Oslo, Norway; 5Department of Neuroscience and Pharmacology, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark; 6Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Nordbyhagen, Norway; 7Department of Biomedicine, University of Bergen, Bergen, Norway; 8Institute of Clinical Medicine, University of Oslo, Faculty of Medicine, Oslo, Norway; 9Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway Abstract Poly(ADP-ribose) polymerase (PARP) enzymes initiate (mt)DNA repair mechanisms and use nicotinamide adenine dinucleotide (NAD+) as energy source. Prolonged PARP activity can drain cellular NAD+ reserves, leading to de-regulation of important molecular processes. Here, we provide evidence of a pathophysiological mechanism that connects mtDNA damage to cardiac *For correspondence: dysfunction via reduced NAD+ levels and loss of mitochondrial function and communication. Using Knut.Huso.Lauritzen@rr-research. a transgenic model, we demonstrate that high levels of mice cardiomyocyte mtDNA damage cause no a reduction in NAD+ levels due to extreme DNA repair activity, causing impaired activation of Competing interests: The NAD+-dependent SIRT3.
[Show full text]
Respiratory Chain Complex I Deficiency Caused by Mitochondrial DNA
European Journal of Human Genetics (2011) 19, 769–775 & 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11 www.nature.com/ejhg ARTICLE Respiratory chain complex I deficiency caused by mitochondrial DNA mutations Helen Swalwell1, Denise M Kirby2, Emma L Blakely1, Anna Mitchell1, Renato Salemi2,6, Canny Sugiana2,3,7, Alison G Compton2, Elena J Tucker2,3, Bi-Xia Ke2, Phillipa J Lamont4, Douglass M Turnbull1, Robert McFarland1, Robert W Taylor1 and David R Thorburn*,2,3,5 Defects of the mitochondrial respiratory chain are associated with a diverse spectrum of clinical phenotypes, and may be caused by mutations in either the nuclear or the mitochondrial genome (mitochondrial DNA (mtDNA)). Isolated complex I deficiency is the most common enzyme defect in mitochondrial disorders, particularly in children in whom family history is often consistent with sporadic or autosomal recessive inheritance, implicating a nuclear genetic cause. In contrast, although a number of recurrent, pathogenic mtDNA mutations have been described, historically, these have been perceived as rare causes of paediatric complex I deficiency. We reviewed the clinical and genetic findings in a large cohort of 109 paediatric patients with isolated complex I deficiency from 101 families. Pathogenic mtDNA mutations were found in 29 of 101 probands (29%), 21 in MTND subunit genes and 8 in mtDNA tRNA genes. Nuclear gene defects were inferred in 38 of 101 (38%) probands based on cell hybrid studies, mtDNA sequencing or mutation analysis (nuclear gene mutations were identified in 22 probands). Leigh or Leigh-like disease was the most common clinical presentation in both mtDNA and nuclear genetic defects.
[Show full text]
NDUFA2 (NM 002488) Human Recombinant Protein Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TP302715 NDUFA2 (NM_002488) Human Recombinant Protein Product data: Product Type: Recombinant Proteins Description: Recombinant protein of human NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 2, 8kDa (NDUFA2) Species: Human Expression Host: HEK293T Tag: C-Myc/DDK Predicted MW: 10.7 kDa Concentration: >50 ug/mL as determined by microplate BCA method Purity: > 80% as determined by SDS-PAGE and Coomassie blue staining Buffer: 25 mM Tris.HCl, pH 7.3, 100 mM glycine, 10% glycerol Preparation: Recombinant protein was captured through anti-DDK affinity column followed by conventional chromatography steps. Storage: Store at -80°C. Stability: Stable for 12 months from the date of receipt of the product under proper storage and handling conditions. Avoid repeated freeze-thaw cycles. RefSeq: NP_002479 Locus ID: 4695 UniProt ID: O43678 RefSeq Size: 726 Cytogenetics: 5q31.3 RefSeq ORF: 297 Synonyms: B8; CD14; CIB8; MC1DN13 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 2 NDUFA2 (NM_002488) Human Recombinant Protein – TP302715 Summary: The encoded protein is a subunit of the hydrophobic protein fraction of the NADH:ubiquinone oxidoreductase (complex 1), the first enzyme complex in the electron transport chain located in the inner mitochondrial membrane, and may be involved in regulating complex I activity or its assembly via assistance in redox processes.
[Show full text]
ARTICLE NDUFA2 Complex I Mutation Leads to Leigh Disease
ARTICLE NDUFA2 Complex I Mutation Leads to Leigh Disease Saskia J.G. Hoefs,1 Cindy E.J. Dieteren,1,2 Felix Distelmaier,1,2,3 Rolf J.R.J. Janssen,1 Andrea Epplen,4 Herman G.P. Swarts,2 Marleen Forkink,1 Richard J. Rodenburg,1 Leo G. Nijtmans,1 Peter H. Willems,2 Jan A.M. Smeitink,1 and Lambert P. van den Heuvel1,* Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed ho- mozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5. Screening of this gene on genomic DNA revealed a mutation that interferes with correct splicing and results in the skipping of exon 2. Exon skipping was confirmed on the mRNA level. The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I. Fur- thermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolariza- tion was (partially) rescued with a baculovirus system expressing the NDUFA2 gene. Introduction deficiencies, suggesting that disease-causing mutations should be found in other genes such as those encoding NADH:ubiquinone oxidoreductase, or complex I, is the the accessory subunits and assembly factors for complex I. first and largest complex of the mitochondrial respiratory The latter mutations have been described in the NDUFAF2 chain. Its function is to liberate and transfer electrons (MIM 609653), NDUFAF1 (MIM 606934), and C6orf66 from NADH to ubiquinone and meanwhile to extract (MIM 611776) genes.15–17 part of their energy to drive proton translocation across Although for the 14 core subunits of complex I, primary the inner mitochondrial membrane and thus to create an roles in electron transfer and proton translocation have electrochemical proton gradient that can be used for the been established, the exact role of the remaining 31 acces- synthesis of ATP.
[Show full text]
Accessory Subunits Are Integral for Assembly and Function of Human Mitochondrial Complex I
Accessory subunits are integral for assembly and function of human mitochondrial complex I David A. Stroud1*, Elliot E. Surgenor1, Luke E. Formosa1,2, Boris Reljic2†, Ann E. Frazier3,4, Marris G. Dibley1, Laura D. Osellame1, Tegan Stait3, Traude H. Beilharz1, David R. Thorburn3-5, Agus Salim6, Michael T. Ryan1* 1Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, 3800, Melbourne, Australia. 2Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University 3086, Melbourne, Australia. 3Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne 3052, Australia 4Department of Pediatrics, University of Melbourne, Melbourne 3052, Australia. 5Victorian Clinical Genetics Services, Royal Children’s Hospital 3052, Melbourne, Australia. 6Department of Mathematics and Statistics, La Trobe University 3086, Melbourne Australia. *Correspondence to: [email protected] and [email protected] †Current address: Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain (RC) and is composed of 44 different subunits in humans, making it one of the largest known multi-subunit membrane protein complexes1. Complex I exists in supercomplex forms with RC complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP2. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson’s disease and aging3-5. Bacterial and human complex I share 14 core subunits essential for enzymatic function, however the role and requirement of the remaining 31 human accessory subunits is unclear1,6.
[Show full text]