Skip to main content
SpringerLink
Log in

Function of Peroxisome in Mammal and Analysis of the Fatty Acid Oxidation System by Photoaffinity Labeling

  • Chapter
  • First Online:
Photoaffinity Labeling for Structural Probing Within Protein

  • 597 Accesses

Abstract

Peroxisomes play an essential role in a number of important metabolic pathways including oxidation of fatty acids, and synthesis of ether phospholipids and bile acids. Long, very long, and branched-chain fatty acid-CoA as well as intermediate metabolites for bile acid synthesis are transported into peroxisomes through ATP-binding cassette (ABC) transporters, ABCD1-3 on the membranes and oxidized by α- and β-oxidation enzymes. Mutation of these transporters and enzymes causes severe peroxisomal disorders. Characterization of molecular mechanism of the substrate transport and the enzyme reaction is an important issue to figure out the role of these proteins in lipid metabolism under physiological and pathological conditions. Recently precise structure of several enzymes involved in peroxisomal fatty acid oxidation has been revealed by the studies based on X-ray crystallography and NMR spectroscopy. However, the molecular mechanisms of these proteins, especially in terms of substrate binding, have not yet been elucidated in detail. Photoaffinity labeling has been a powerful tool to find specific region for the binding of the substrate using a ligand with a photoactivatable group. Here, we first review biogenesis and function of peroxisome, and then focus our attention to molecular recognition of substrate by peroxisomal proteins including ABC transporters by photoaffinity labeling.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ABC:

ATP-binding cassette

DHA:

Docosahexaenoic acid

DHCA:

Dihydroxycholestanoic acid

ER:

Endoplasmic reticulum

LCFA:

Long-chain fatty acid

PBD:

Peroxisome biogenesis disorder

PMP:

Peroxisomal membrane protein

PTS:

Peroxisome targeting signal

RCDP:

Rhizomelic chondrodysplasia punctata

THCA:

Trihydroxycholestanoic acid

VLCFA:

Very long-chain fatty acid

X-ALD:

X-linked adrenoleukodystrophy

References

  • Agrawal G, Subramani S (2016) De novo peroxisome biogenesis: evolving concepts and conundrums. Biochim Biophys Acta 1863:892–901

    Article  CAS  PubMed  Google Scholar 

  • Aller SG, Yu J, Ward A, Weng Y, Chittaboina S, Zhuo R, Harrell PM, Trinh YT, Zhang Q, Urbatsch IL, Chang G (2009) Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding. Science 323:1718–1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berger J, Dorninger F, Forss-Petter S, Kunze M (2016) Peroxisomes in brain development and function. Biochim Biophys Acta 1863:934–955

    Article  CAS  PubMed  Google Scholar 

  • Bowen P, Lee CS, Zellweger H, Lindenberg R (1964) A familial syndrome of multiple congenital defects. Bull Johns Hopkins Hosp 114:402–414

    CAS  PubMed  Google Scholar 

  • Bowers WE (1998) Christian de Duve and the discovery of lysosomes and peroxisomes. Trends Cell Biol 8:330–333

    Article  CAS  PubMed  Google Scholar 

  • Brendel C, Scharenberg C, Dohse M, Robey RW, Bates SE, Shukla S, Ambudkar SV, Wang Y, Wennemuth G, Burchert A, Boudriot U, Neubauer A (2007) Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia 21:1267–1275

    Article  CAS  PubMed  Google Scholar 

  • Brunner R, Ng CL, Aissaoui H, Akabas MH, Boss C, Brun R, Callaghan PS, Corminboeuf O, Fidock DA, Frame IJ, Heidmann B, Le Bihan A, Jeno P, Mattheis C, Moes S, Muller IB, Paguio M, Roepe PD, Siegrist R, Voss T, Welford RW, Wittlin S, Binkert C (2013) UV-triggered affinity capture identifies interactions between the plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells. J Biol Chem 288:22576–22583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu BB, Liao YC, Qi W, Xie C, Du X, Wang J, Yang H, Miao HH, Li BL, Song BL (2015) Cholesterol transport through lysosome-peroxisome membrane contacts. Cell 161:291–306

    Article  CAS  PubMed  Google Scholar 

  • Dawson RJ, Locher KP (2006) Structure of a bacterial multidrug ABC transporter. Nature 443:180–185

    Article  CAS  PubMed  Google Scholar 

  • De Duve C, Baudhuin P (1966) Peroxisomes (microbodies and related particles). Physiol Rev 46:323–357

    PubMed  Google Scholar 

  • Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC (2010) Peroxisomes are signaling platforms for antiviral innate immunity. Cell 141:668–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebberink MS, Koster J, Visser G, Spronsen F, Stolte-Dijkstra I, Smit GP, Fock JM, Kemp S, Wanders RJ, Waterham HR (2012) A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11beta gene. J Med Genet 49:307–313

    Article  CAS  PubMed  Google Scholar 

  • Ferdinandusse S, Jimenez-Sanchez G, Koster J, Denis S, Van Roermund CW, Silva-Zolezzi I, Moser AB, Visser WF, Gulluoglu M, Durmaz O, Demirkol M, Waterham HR, Gokcay G, Wanders RJ, Valle D (2015) A novel bile acid biosynthesis defect due to a deficiency of peroxisomal ABCD3. Hum Mol Genet 24:361–370

    Article  CAS  PubMed  Google Scholar 

  • Ferdinandusse S, Ylianttila MS, Gloerich J, Koski MK, Oostheim W, Waterham HR, Hiltunen JK, Wanders RJ, Glumoff T (2006) Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. Am J Hum Genet 78:112–24

    Google Scholar 

  • Fourcade S, Ruiz M, Camps C, Schluter A, Houten SM, Mooyer PA, Pampols T, Dacremont G, Wanders RJ, Giros M, Pujol A (2009) A key role for the peroxisomal ABCD2 transporter in fatty acid homeostasis. Am J Physiol Endocrinol Metab 296:E211–E221

    Article  CAS  PubMed  Google Scholar 

  • Francisco T, Rodrigues TA, Pinto MP, Carvalho AF, Azevedo JE, Grou CP (2014) Ubiquitin in the peroxisomal protein import pathway. Biochimie 98:29–35

    Article  CAS  PubMed  Google Scholar 

  • Fujiki Y, Nashiro C, Miyata N, Tamura S, Okumoto K (2012) New insights into dynamic and functional assembly of the AAA peroxins, Pex1p and Pex6p, and their membrane receptor Pex26p in shuttling of PTS1-receptor Pex5p during peroxisome biogenesis. Biochim Biophys Acta 1823:145–149

    Article  CAS  PubMed  Google Scholar 

  • Fujita Y, Noguchi K, Suzuki T, Katayama K, Sugimoto Y (2013) Biochemical interaction of anti-HCV telaprevir with the ABC transporters P-glycoprotein and breast cancer resistance protein. BMC Res Notes 6:445

    Article  PubMed  PubMed Central  Google Scholar 

  • Genin EC, Geillon F, Gondcaille C, Athias A, Gambert P, Trompier D, Savary S (2011) Substrate specificity overlap and interaction between adrenoleukodystrophy protein (ALDP/ABCD1) and adrenoleukodystrophy-related protein (ALDRP/ABCD2). J Biol Chem 286:8075–8084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisniewski HK, Ritch RH, Norton WT, Rapin I, Gartner LM (1973) Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 182:62–64

    Article  CAS  PubMed  Google Scholar 

  • Guimaraes CP, Sa-Miranda C, Azevedo JE (2005) Probing substrate-induced conformational alterations in adrenoleukodystrophy protein by proteolysis. J Hum Genet 50:99–105

    Article  CAS  PubMed  Google Scholar 

  • Haapalainen AM,Koski MK, Qin YM, Hiltunen JK, Glumoff T (2003) Binary structure of the two-domain (3R)-hydroxyacyl-CoA dehydrogenase from rat peroxisomal multifunctional enzyme type 2 at 2.38 Å resolution. Structure 11:87–97

    Google Scholar 

  • Haataja TJ, Koski MK, Hiltunen JK, Glumoff T (2011) Peroxisomal multifunctional enzyme type 2 from the fruitfly: dehydrogenase and hydratase act as separate entities, as revealed by structure and kinetics. Biochem J 435:771–781

    Article  CAS  PubMed  Google Scholar 

  • Hasan S, Platta HW, Erdmann R (2013) Import of proteins into the peroxisomal matrix. Front Physiol 4:261

    Article  PubMed  PubMed Central  Google Scholar 

  • Hatanaka Y (2015) Development and leading-edge application of innovative photoaffinity labeling. Chem Pharm Bull (Tokyo) 63:1–12

    Article  CAS  Google Scholar 

  • Hozoji-Inada M, Munehira Y, Nagao K, Kioka N, Ueda K (2011) Liver X receptor beta (LXRbeta) interacts directly with ATP-binding cassette A1 (ABCA1) to promote high density lipoprotein formation during acute cholesterol accumulation. J Biol Chem 286:20117–20124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huber N, Guimaraes S, Schrader M, Suter U, Niemann A (2013) Charcot-Marie-tooth disease-associated mutants of GDAP1 dissociate its roles in peroxisomal and mitochondrial fission. EMBO Rep 14:545–552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huyghe S, Mannaerts GP, Baes M, Van Veldhoven PP (2006) Peroxisomal multifunctional protein-2: the enzyme, the patients and the knockout mouse model. Biochim Biophys Acta 1761:973–994

    Article  CAS  PubMed  Google Scholar 

  • Kashiwayama Y, Morita M, Kamijo K, Imanaka T (2002) Nucleotide-induced conformational changes of PMP70, an ATP binding cassette transporter on rat liver peroxisomal membranes. Biochem Biophys Res Commun 291:1245–1251

    Article  CAS  PubMed  Google Scholar 

  • Kashiwayama Y, Tomohiro T, Narita K, Suzumura M, Glumoff T, Hiltunen JK, Van Veldhoven PP, Hatanaka Y, Imanaka T (2010) Identification of a substrate-binding site in a peroxisomal beta-oxidation enzyme by photoaffinity labeling with a novel palmitoyl derivative. J Biol Chem 285:26315–26325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kodan A, Yamaguchi T, Nakatsu T, Sakiyama K, Hipolito CJ, Fujioka A, Hirokane R, Ikeguchi K, Watanabe B, Hiratake J, Kimura Y, Suga H, Ueda K, Kato H (2014) Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog. Proc Natl Acad Sci U S A 111:4049–4054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuang YH, Patel JP, Sodani K, Wu CP, Liao LQ, Patel A, Tiwari AK, Dai CL, Chen X, Fu LW, Ambudkar SV, Korlipara VL, Chen ZS (2012) OSI-930 analogues as novel reversal agents for ABCG2-mediated multidrug resistance. Biochem Pharmacol 84:766–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lazarow PB, De Duve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci U S A 73(6):2043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mangroo D, Steele L, Rachubinski RA, Gerber GE (1993) Specific labeling of Candida tropicalis peroxisomal proteins with photoreactive fatty-acid derivatives. Biochim Biophys Acta 1168:280–284

    Article  CAS  PubMed  Google Scholar 

  • Masuda S, Tomohiro T, Yamaguchi S, Morimoto S, Hatanaka Y (2015) Structure-assisted ligand-binding analysis using fluorogenic photoaffinity labeling. Bioorg Med Chem Lett 25(8):1675

    Article  CAS  PubMed  Google Scholar 

  • Morita M, Imanaka T (2012) Peroxisomal ABC transporters: structure, function and role in disease. Biochim Biophys Acta 1822:1387–1396

    Article  CAS  PubMed  Google Scholar 

  • Patel A, Tiwari AK, Chufan EE, Sodani K, Anreddy N, Singh S, Ambudkar SV, Stephani R, Chen ZS (2013) PD173074, a selective FGFR inhibitor, reverses ABCB1-mediated drug resistance in cancer cells. Cancer Chemother Pharmacol 72:189–199

    Article  CAS  PubMed  Google Scholar 

  • Pleban K, Kopp S, Csaszar E, Peer M, Hrebicek T, Rizzi A, Ecker GF, Chiba P (2005) P-glycoprotein substrate binding domains are located at the transmembrane domain/transmembrane domain interfaces: a combined photoaffinity labeling-protein homology modeling approach. Mol Pharmacol 67:365–374

    Article  CAS  PubMed  Google Scholar 

  • Rajasekharan R, Marians RC, Shockey JM, Kemp JD (1993) Photoaffinity labeling of acyl-CoA oxidase with 12-azidooleoyl-CoA and 12-[(4-azidosalicyl)amino]dodecanoyl-CoA. Biochemistry 32:12386–12391

    Article  CAS  PubMed  Google Scholar 

  • Rhodin JAG (1954) Correlation of ultrastructural organization: and function in normal and experimentally changed proximal convoluted tubule cells of the mouse kidney: an electron microscopic study. Karolinska Institutet

    Google Scholar 

  • van Roermund CW, Visser WF, Ijlst L, Waterham HR, Wanders RJ (2011) Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid beta-oxidation. Biochim Biophys Acta 1811:148–152

    Article  PubMed  Google Scholar 

  • Rucktaschel R, Girzalsky W, Erdmann R (2011) Protein import machineries of peroxisomes. Biochim Biophys Acta 1808:892–900

    Article  PubMed  Google Scholar 

  • Sato Y, Shibata H, Nakatsu T, Nakano H, Kashiwayama Y, Imanaka T, Kato H (2010) Structural basis for docking of peroxisomal membrane protein carrier Pex19p onto its receptor Pex3p. EMBO J 29:4083–4093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla S, Robey RW, Bates SE, Ambudkar SV (2009) Sunitinib (Sutent, SU11248), a small-molecule receptor tyrosine kinase inhibitor, blocks function of the ATP-binding cassette (ABC) transporters P-glycoprotein (ABCB1) and ABCG2. Drug Metab Dispos 37:359–365

    Article  CAS  PubMed  Google Scholar 

  • Tanaka AR, Tanabe K, Morita M, Kurisu M, Kasiwayama Y, Matsuo M, Kioka N, Amachi T, Imanaka T, Ueda K (2002) ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP70 (ABCD3) and adrenoleukodystrophy protein (ABCD1). J Biol Chem 277:40142–40147

    Article  CAS  PubMed  Google Scholar 

  • Tomohiro T, Inoguchi H, Masuda S, Hatanaka Y (2013) Affinity-based fluorogenic labeling of ATP-binding proteins with sequential photoactivatable cross-linkers. Bioorg Med Chem Lett 23:5605–5608

    Article  CAS  PubMed  Google Scholar 

  • Vamecq J, Cherkaoui-Malki M, Andreoletti P, Latruffe N (2014) The human peroxisome in health and disease: the story of an oddity becoming a vital organelle. Biochimie 98:4–15

    Article  CAS  PubMed  Google Scholar 

  • Verheijden S, Beckers L, De Munter S, Van Veldhoven PP,Baes M (2014) Central nervous system pathology in MFP2 deficiency: insights from general and conditional knockout mouse models. Biochimie 98:119–26

    Google Scholar 

  • Wanders RJ, Komen J, Ferdinandusse S (2011) Phytanic acid metabolism in health and disease. Biochim Biophys Acta 1811:498–507

    Article  CAS  PubMed  Google Scholar 

  • Wanders RJ, Waterham HR, Ferdinandusse S (2016) Metabolic interplay between peroxisomes and other subcellular organelles including mitochondria and the endoplasmic reticulum. Front Cell Dev Biol 3:83

    Article  PubMed  PubMed Central  Google Scholar 

  • Ward A, Reyes CL, Yu J, Roth CB, Chang G (2007) Flexibility in the ABC transporter MsbA: alternating access with a twist. Proc Natl Acad Sci U S A 104:19005–19010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV (2007) A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med 356:1736–1741

    Article  CAS  PubMed  Google Scholar 

  • Waterham HR, Ferdinandusse S, Wanders RJ (2016) Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta 1863:922–933

    Article  CAS  PubMed  Google Scholar 

  • Wu CP, Shukla S, Calcagno AM, Hall MD, Gottesman MM, Ambudkar SV (2007) Evidence for dual mode of action of a thiosemicarbazone, NSC73306: a potent substrate of the multidrug resistance linked ABCG2 transporter. Mol Cancer Ther 6:3287–3296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported in part by a Grant-in-Aid for Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20590054, 23590072, 26460063). Pacific Edit reviewed the manuscript prior to submission.

Author information

Authors and Affiliations

  1. Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Tsuneo Imanaka, Kosuke Kawaguchi & Masashi Morita

  2. Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1, Hirokoshinkai, Kure, Hiroshima, 737-0112, Japan

    Tsuneo Imanaka

Authors
  1. Tsuneo Imanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kosuke Kawaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masashi Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tsuneo Imanaka .

Editor information

Editors and Affiliations

  1. University of Toyama, Toyama, Japan

    Yasumaru Hatanaka

  2. Graduate School of Agriculture, Hokkaido University, Sapporo, Hokkaido, Japan

    Makoto Hashimoto

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Japan KK

About this chapter

Cite this chapter

Imanaka, T., Kawaguchi, K., Morita, M. (2017). Function of Peroxisome in Mammal and Analysis of the Fatty Acid Oxidation System by Photoaffinity Labeling. In: Hatanaka, Y., Hashimoto, M. (eds) Photoaffinity Labeling for Structural Probing Within Protein. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56569-7_10

Download citation

Publish with us

Policies and ethics

Search

Navigation