Skip to main content
SpringerLink
Log in

Avian UCP: The Killjoy in the Evolution of the Mitochondrial Uncoupling Proteins

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Abstract

The understanding of mitochondrial functioning is of prime importance since it combines the production of energy as adenosine triphosphate (ATP) with an efficient chain of redox reactions, but also with the unavoidable production of reactive oxygen species (ROS) involved in aging. Mitochondrial respiration may be uncoupled from ATP synthesis by a proton leak induced by the thermogenic uncoupling protein 1 (UCP1). Mild uncoupling activity, as proposed for UCP2, UCP3, and avian UCP could theoretically control ROS production, but the nature of their transport activities is far from being definitively understood. The recent discovery of a UCP1 gene in fish has balanced the evolutionary view of uncoupling protein history. The thermogenic proton transport of mammalian UCP1 seems now to be a late evolutionary characteristic and the hypothesis that ancestral UCPs may carry other substrates is tempting. Using in silico genome analyses among taxa and a biochemical approach, we present a detailed phylogenetic analysis of UCPs and investigate whether avian UCP is a good candidate for pleiotropic mitochondrial activities, knowing that only one UCP has been characterized in the avian genome, unlike all other vertebrates. We show, here, that the avian class seems to be the only vertebrate lineage lacking two of the UCP1/2/3 homologues present in fish and mammals. We suggest, based on phylogenetic evidence and synteny of the UCP genes, that birds have lost UCP1 and UCP2. The phylogeny also supports the history of two rounds of duplication during vertebrate evolution. The avian uncoupling protein then represents a unique opportunity to explore how UCPs’ activities are controlled, but also to understand why birds exhibit such a particular relationship between high metabolism and slow rate of aging.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abe T, Mujahid A, Sato K, Akiba Y, Toyomisu M (2006) Possible role of avian uncoupling protein in down-regulating mitochondrial superoxide production in skeletal muscle of fasted chickens. FEBS Lett 580:4815–4822

    Article  PubMed  CAS  Google Scholar 

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    PubMed  CAS  Google Scholar 

  • Andreyev AY, Bondareva TO, Dedukhova VI, Mokhova EN, Skulachev VP, Tsofina LM, Volkov NI, Vygodina TV (1989) The ATP/ADP-antiporter is involved in the uncoupling effect of fatty acids on mitochondria. Eur J Biochem 182:585–592

    Article  PubMed  Google Scholar 

  • Aquila H, Link T, Klingenberg M (1985) The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane. EMBO J 4:2369–2376

    PubMed  CAS  Google Scholar 

  • Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581

    PubMed  CAS  Google Scholar 

  • Benistant C, Duchamp C, Cohen-Adad F, Rouanet J-L, Barré H (1998) Increased in vitro fatty acids supply and cellular transport capacities in cold-acclimated ducklings (Cairina moschata). Am J Physiol 275:683–690

    Google Scholar 

  • Block BA (1994) Thermogenesis in muscle. Annu Rev Physiol 56:535–577

    Article  PubMed  CAS  Google Scholar 

  • Bouillaud F, Couplan E, Pecqueur C, Ricquier D (2001) Homologues of the uncoupling protein from brow adipose tissue (UCP1): UCP2, UCP3, BMCP1 and UCP4. Biochim Biophys Acta 1504:107–119

    Article  PubMed  CAS  Google Scholar 

  • Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35:811–820

    Article  PubMed  CAS  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359

    Article  PubMed  CAS  Google Scholar 

  • Castresana J (2000). Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 17:540–552

    PubMed  CAS  Google Scholar 

  • Collin A, Buyse J, Van As P, Darras VM, Malheiros RD, Moraes VMB, Reyns GE, Taouis M, Decuypere E (2003) Cold-induced enhancement of avian uncoupling protein expression, heat production, and triiodothyronine concentrations in broiler chicks. Gen Comp Endocrinol 130:70–77

    Article  PubMed  CAS  Google Scholar 

  • Criscuolo F, Gonzalez-Barroso MM, Bouillaud F, Ricquier D, Miroux B, Sorci G (2005a) Mitochondrial uncoupling proteins: new perspectives for evolutionary ecologists. Am Nat 166:686–699

  • Criscuolo F, Gonzalez-Barroso MM, Ricquier D, Le Maho Y, Bouillaud F (2005b) Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radicals damage. Proc R Soc Lond B Biol Sci 272:803–810

    Google Scholar 

  • Dridi S, Onagbesan O, Swennen Q, Buyse J, Decuypere E, Taouis M (2005) Gene expression, tissue distribution and potential physiological role of uncoupling protein in avian species. Comp Biochem Physiol A 139:273–283

    Google Scholar 

  • Echtay KS, Liu Q, Caskey T, Winkler E, Frischmuth K, Bienengraber M, Klingenberg M (1999) Regulation of UCP3 by nucleotides is different from regulation of UCP1. FEBS Lett 450:8–12

    Article  PubMed  CAS  Google Scholar 

  • Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32(5):1792–1797

    Article  PubMed  CAS  Google Scholar 

  • Emre Y, Hurtaud C, Nübel T, Criscuolo F, Ricquier D, Cassard-Doulcier AM (2007) Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages. Biochem J 402:271–278

    Article  PubMed  CAS  Google Scholar 

  • Enerback S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kosak LP (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 381:90–94

    Article  Google Scholar 

  • Evock-Clover CM, Poch SM, Richards MP, Ashwell CM, McMurtry JP (2002) Expression of an uncoupling protein gene homolog in chickens. Comp Biochem Physiol A 133:345–358

    Article  Google Scholar 

  • Feng J, Bussière F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1:633–644

    Article  PubMed  CAS  Google Scholar 

  • Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15:269–272

    Article  PubMed  CAS  Google Scholar 

  • Fridell Y-WC, Sanchez-Blanco A, Silvia BA, Helfand SL (2005) Targeted expression f the human uncoupling protein 2 (hUCP2) to adult neurons extends life span in the fly. Cell Metab 1:145–152

    Article  PubMed  CAS  Google Scholar 

  • Garlid KD, Jaburek M, Jezek P, Varecha M (2000) How do uncoupling proteins uncouple? Biochim Biophys Acta 1459:383–389

    Article  PubMed  CAS  Google Scholar 

  • Garlid KD, Paucek P (2003) Mitochondrial potassium transport: the K+ cycle. Biochim Biophys Acta 1606:23–41

    Article  PubMed  CAS  Google Scholar 

  • Garlid KD, Dos Santos P, Xie Z, Paucek P (2003) Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K+ channel in cardiac function and cardioprotection. Biochim Biophys Acta 1606:1–21

    Article  PubMed  CAS  Google Scholar 

  • Guindon S, Gascuel O (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52(5):696–704

    Article  PubMed  Google Scholar 

  • Guindon S, Lethiec F, Duroux P, Gascuel O (2005) PHYML Online–a web server for fast maximum likelihood-based phylogenetic inference. Nucleic Acids Res 33(Web Server issue):W557–9

    Article  PubMed  CAS  Google Scholar 

  • Haguenauer A, Raimbault S, Masscheleyn S, Gonzalez-Barroso M, Criscuolo F, Plamondon J, Bouillaud F, Miroux B, Ricquier D, Richard D, Bouillaud F, Pecqueur C (2005) A new renal mitochondrial carrier, KMCP1, is up-regulated during tubular cell regeneration and induction of antioxidant enzymes. J Biol Chem 280:22036–22043

    Article  PubMed  CAS  Google Scholar 

  • Hanàk P, Jezek P (2001) Mitochondrial uncoupling protein and phylogenesis – UCP4 as the ancestral uncoupling protein. FEBS Lett 495:137–141

    Article  PubMed  Google Scholar 

  • Hokamp K, McLysaght A, Wolfe KH (2003) The 2R hypothesis and the human genome sequence. J Struct Funct Genomics 3:95–110

    Article  PubMed  CAS  Google Scholar 

  • Holmes DJ, Austad SN (1995) Birds as animal models for the comparative biology of aging: a prospectus. J Gerontol Biol Sci 50A:B59–B66

    Google Scholar 

  • Huelsenbeck JP, Ronquist F (2001) MrBayes: Bayesian inference of phylogeny. Bioinformatics 17:754–755

    Article  PubMed  CAS  Google Scholar 

  • Jastroch M, Wuertz S, Werner K, Klingenspor M (2005) Uncoupling protein 1 in fish uncovers an ancient evolutionary history of mammalian nonshivering thermogenesis. Physiol Genomics 22: 150–156

    Article  PubMed  CAS  Google Scholar 

  • Jezek P, Borecky J (1998) Mitochondrial uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates. Am J Physiol 275:496–504

    Google Scholar 

  • Keane TM, Creevey CJ, Pentony MM, Naughton TJ, O’McInerney J (2006) Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 6:29

    Article  PubMed  Google Scholar 

  • Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238

    Article  PubMed  CAS  Google Scholar 

  • Klingenberg M (1990) Mechanism and evolution of the uncoupling protein of brown adipose tissue. Trends Biochem Sci 15:108–112

    Article  PubMed  CAS  Google Scholar 

  • Lithgow GJ, Kirkwood TBL (1996) Mechanisms and evolution of aging. Science 273:80

    Article  PubMed  CAS  Google Scholar 

  • Mair W, Piper MDW, Partridge L (2005) Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3:1305–1311

    Article  CAS  Google Scholar 

  • Mao W, Yu XX, Zhong A, Li W, Brush J, Sherwood SW, Adams SH, Pan G (1999) UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett 443:326–330

    Article  PubMed  CAS  Google Scholar 

  • Mozo J, Ferry G, Studeny A, Pecqueur C, Rodriguez M, Boutin JA, Bouillaud F (2006) Expression of UCP3 in CHO cells does not cause uncoupling but controls mitochondrial activity in presence of glucose. Biochem J 393:431–439

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG, Grav HJ, Lindberg O (1972) Mitochondrial from hamster brown-adipose tissue. Regulation of respiration in vitro by variations in volume of the matrix compartment. Eur J Biochem 31:526–533

    Article  PubMed  CAS  Google Scholar 

  • Pecqueur C, Cassard-Doulcier AM, Raimbault S, Miroux B, Fleury C, Gelly C, Bouillaud F, Ricquier D (1999) Functional organization of the human uncoupling protein-2 gene, and juxtaposition to the uncoupling protein-3 gene. Biochem Biophys Res Commun 255:40–46

    Article  PubMed  CAS  Google Scholar 

  • Raimbault S, Dridi S, Denjean F, Lachuer J, Couplan E, Bouillaud F, Duchamp C, Taouis M, Ricquier D (2001) An uncoupling protein homologue putatively involved in facultative muscle thermogenesis in birds. Biochem J 353:441–444

    Article  PubMed  CAS  Google Scholar 

  • Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 345:161–179

    Article  PubMed  CAS  Google Scholar 

  • Rose RW, West AK, Ye JM, McCormick GH, Colquhoun EQ (1999) Nonshivering thermogenesis in a marsupial (the Tasmanian bettong Bettongia gaimardi) is not attributable to brown adipose tissue. Physiol Biochem Zool 72:699–704

    Article  PubMed  CAS  Google Scholar 

  • Sidow A (1996) Gen(om)e duplications in the evolution of early vertebrates. Curr Opin Genet Dev 6:715–720

    Article  PubMed  CAS  Google Scholar 

  • Talbot DA, Duchamp C, Rey B, Hanuise N, Rouanet J-L, Sibille B, Brand MD (2004) Uncoupling protein and ATP/ADP carrier increase mitochondrial proton conductance after cold adaptation of king penguins. J Physiol 558:123–135

    Article  PubMed  CAS  Google Scholar 

  • Talbot DA, Hanuise N, Rey B, Rouanet J-L, Duchamp C, Brand MD (2003) Superoxide activates a GDP-sensitive proton conductance in skeletal muscle mitochondria from king penguin (Aptenodytes patagonicus). Biochem Biophys Res Commun 312:983–988

    Article  PubMed  CAS  Google Scholar 

  • Vianna CR, Hagen T, Zhang CY, Bachman E, Boss O, Gereben B, Moriscot AS, Lowell BB, Bicudo JEPW, Bianco AC (2001) Cloning and characterization of an uncoupling homolog in hummingbirds. Physiol Genomics 5:137–145

    PubMed  CAS  Google Scholar 

  • Vidal-Puig AJ, Solanes G, Grujic D, Flier JS, Lowell BB (1997) UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochem Biophys Res Commun 235:79–82

    Article  PubMed  CAS  Google Scholar 

  • Zera AJ, Harshman LG (2001) The physiology of life history trade-offs in animals. Annu Rev Ecol Syst 32:95–126

    Article  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Pr G. Lecointre and H. Gachot-Neveu for fruitful discussions on the roles and phylogeny of uncoupling proteins and help with phylogenic analysis, and A. Haguenauer for the sequence of avian BMCP1, discovered by S. Raimbault, to whose memory this paper is dedicated.

Author information

Authors and Affiliations

  1. CNRS-UPR 9078, Faculté de Médecine Descartes Paris 5 - Necker, 156 rue de Vaugirard, 75730, Paris, Cedex 15, France

    Yalin Emre, Corinne Hurtaud, Daniel Ricquier, Frederic Bouillaud & François Criscuolo

  2. Institute of Biomedical and Life Sciences, Division of Environmental and Evolutionary Biology, University of Glasgow, Glasgow, G12 8QQ, UK

    Joseph Hughes & François Criscuolo

Authors
  1. Yalin Emre
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Corinne Hurtaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Ricquier
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frederic Bouillaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joseph Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. François Criscuolo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to François Criscuolo.

Electronic supplementary material

Annex

Annex

NCBI reference number of protein sequences used for phylogenic inference analysis.

ANT Ath (BAB11273); ANT Dme (Q26365), ANT Hsa1 (P12235), ANT Ocu (O46373), ANT Ssc1 (AAD20940), ANT Gga (BAC15373), ANT Hsa2 (P05141), ANT Hsa3 (P12236), ANT Cfa (XP532844), ANT Ssc3 (Q6QRN9), BMCP1 Hsa (O95258), BMCP1 Mmu (Q922B2), BMCP1 Rno (CAC20901), KMCP1 Has (see ref. 6), BMCP Dme A (AAN11881), BMCP Dme B (NP 729138), UCP4 Dme (AAF48769), UCP4 Bta (XP 604084), UCP4b Rno (CAC20889), UCP4c Rno (CAC20900), UCP4a Rno (CAC20898), UCP4Xla (AAO26203), UCP Stu (CAB60277), UCP Ath (AAL07121), UCP1 Cfa (Q9GM21), UCP1 Hsa (P25874), UCP1 Bta (P10861), UCP1 Ocu (P14271), UCP1 Mmu (P12242), UCP1 Rno (NP036814), UCP1 Psu (AAG33983), UCP1 Mau (P04575), UCP2 Pma (AAL92117), UCP3 Afl (AAS45212), UCP3 Psu (AAG33985), UCP3 Mmu (NP 033490), UCP3 Rno (NP037299), UCP3 Hsa (NP003347), UCP3 Bta (077792), UCP3 Ssc (NP999214), UCP3 Cfa (Q9N2I9), UCP Ema (AAK16829), UCP Apa (AAT05613), UCP Gga (BAC 15532), UCP Mga (AAL28138), UCP3 Dre (see ref. 12), UCP1 Dre (see ref. 12), UCP2 Ssc (O97562), UCP2 Mmu (P70406), UCP2 Rno (NP062227), UCP2 Psu (AAG33984), UCP2 Hsa (NP003346), UCP2 Cfa (Q9N2J1), UCP2 Sma (AAP45779), UCP2 Afl (see ref. 34), UCP2 Xla (AAH44682), UCP2 Cca (Q9W725), UCP2 Dre (Q9W720).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Emre, Y., Hurtaud, C., Ricquier, D. et al. Avian UCP: The Killjoy in the Evolution of the Mitochondrial Uncoupling Proteins. J Mol Evol 65, 392–402 (2007). https://doi.org/10.1007/s00239-007-9020-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00239-007-9020-1

Keywords

Search

Navigation