Skip to main content

l-Carnitine is essential to β-oxidation of quarried fatty acid from mitochondrial membrane by PLA2


Mitochondrial β-oxidation is an important system involved in the energy production of various cells. In this system, the function of l-carnitine is essential for the uptake of fatty acids to mitochondria. However, it is unclear whether or not endogenous respiration, ADP-induced O2 consumption without substrates, is caused by l-carnitine treatment. In this study, we investigated whether l-carnitine is essential to the β-oxidation of quarried fatty acids from the mitochondrial membrane by phospholipase A2 (PLA2) using isolated mitochondria from the liver of rats. Intact mitochondria were incubated in a medium containing Pi, CoA and l-carnitine. The effect of l-carnitine treatment on ADP-induced mitochondrial respiration was observed without exogenous respiratory substrate. Increase in mitochondrial respiration was induced by treatment with l-carnitine in a concentration-dependent manner. Treatment with rotenone, a complex I blocker, completely inhibited ADP-induced oxygen consumption even in the presence of l-carnitine. Moreover, the l-carnitine dependent ADP-induced mitochondrial oxygen consumption did not increase when PLA2 inhibitors were treated before ADP treatment. The l-carnitine-dependent ADP-induced oxygen consumption did contribute to ATP productions but not heat generation via an uncoupling system. These results suggest that l-carnitine might be essential to the β-oxidation of quarried fatty acids from the mitochondrial membrane by PLA2.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6



Carnitine palmitoyl transferase I


Organic cation/carnitine transporter 2

PLA2 :

Phospholipase A2


Coenzyme A






Mefenamic acid


Aristolochic acid


Ethylene glycol tetraacetic acid


Ratio of respiratory control


Bovine serum albumin

iPLA2 :

Ca2+-independent PLA2


  1. Bremer J (1983) Carnitine—metabolism and functions. Physiol Rev 63:1420–1480

    CAS  PubMed  Google Scholar 

  2. Li MX, Yoshida G, Horiuchi M, Kobayashi K, Saheki T (2006) Prolonged effect of single carnitine administration on fasted carnitine-deficient JVS mice regarding their locomotor activity and energy expenditure. Biochim Biophys Acta 1761:1191–1199

    CAS  PubMed  Google Scholar 

  3. Kerner J, Parland WK, Minkler PE, Hoppel CL (2008) Rat liver mitochondrial carnitine palmitoyltransferase-I, hepatic carnitine, and malonyl-CoA: effect of starvation. Arch Physiol Biochem 114:161–170

    Article  CAS  PubMed  Google Scholar 

  4. Oyanagi E, Yano H, Kato Y, Fujita H, Utsumi K, Sasaki J (2008) l-carnitine suppresses oleic acid-induced membrane permeability transition of mitochondria. Cell Biochem Funct 26:778–786. doi:10.1002/cbf.1506

    Article  CAS  PubMed  Google Scholar 

  5. Kim JS, Southard JH (2000) Effect of phospholipase A2 inhibitors on the release of arachidonic acid and cell viability in cold-stored hepatocytes. Cryobiology 40:27–35

    Article  CAS  PubMed  Google Scholar 

  6. Furuno T, Kanno T, Arita K, Asami M, Utsumi T, Doi Y, Inoue M, Utsumi K (2001) Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 62:1037–1046. doi:10.1016/S0006-2952(01)00745-6

    Article  CAS  PubMed  Google Scholar 

  7. Reda E, D’Iddio S, Nicolai R, Benatti P, Calvani M (2003) The carnitine system and body composition. Acta Diabetol 40:S106–S113. doi:10.1007/s00592-003-0040-z

    Article  CAS  PubMed  Google Scholar 

  8. Javadov S, Karmazn M (2007) Mitochondrial permeability transition pore opening as an endpoint to initiate cell death and as a putative target for cardioprotection. Cell Physiol Biochem 20:1–22. doi:10.1159/000103747

    Article  CAS  PubMed  Google Scholar 

  9. Gadd ME, Broekemeier KM, Crouser ED, Kumar J, Graff G, Pfeiffer DR (2006) Mitochondrial iPLA2 activity modulates the release of cytochrome c from mitochondria and influences the permeability transition. J Biol Chem 281:6931–6939. doi:10.1074/jbc.M510845200

    Article  CAS  PubMed  Google Scholar 

  10. Arita K, Kobuchi H, Utsumi T, Takehara Y, Akiyama J, Horton AA, Utsumi K (2001) Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids. Biochem Pharmacol 62:821–828. doi:10.1016/S0006-2952(01)00723-7

    Article  CAS  PubMed  Google Scholar 

  11. Kanno T, Sato EE, Muranaka S, Fujita H, Fujuwara T, Utsumi T, Inoue M, Utsumi K (2004) Oxidative stress underlies the mechanism for Ca(2+)-induced permeability transition of mitochondria. Free Radic Res 38:27–35

    Article  CAS  PubMed  Google Scholar 

  12. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  13. Nishimura M, Okimura Y, Fujita H, Yano H, Lee J, Suzaki E, Inoue M, Utsumi K, Sasaki J (2008) Mechanism of 3-nitropropionic acid-induced membrane permeability transition of isolated mitochondria and its suppression by l-carnitine. Cell Biochem Funct 26:881–891. doi:10.1002/cbf.1521

    Article  CAS  PubMed  Google Scholar 

  14. Bielefeld DR, Vary TC, Neely JR (1985) Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscle. J Mol Cell Cardiol 17:619–625. doi:10.1016/S0022-2828(85)80030-4

    Article  CAS  PubMed  Google Scholar 

  15. Murthy MSR, Pande SV (1987) Malonyl-CoA binding site and the overt carnitine palmitoyltransferase activity reside on the opposite sides of the outer mitochondrial membrane. Proc Natl Acad Sci USA 84:378–382

    Article  CAS  PubMed  Google Scholar 

  16. Fraser F, Zammit VA (1998) Enrichment of carnitine palmitoyltransferases I and II in the contact sites of rat liver mitochondria. Biochem J 329:225–229

    CAS  PubMed  Google Scholar 

  17. Fraser F, Padovese R, Zammit VA (2001) Distinct kinetics of carnitine palmitoyltransferase I in contact sites and outer membranes of rat liver mitochondria. J Biol Chem 276:20182–20185. doi:10.1074/jbc.M101078200

    Article  CAS  PubMed  Google Scholar 

  18. Dlasková A, Hlavatá L, Jezek J, Jezek P (2008) Mitochondrial complex I superoxide production is attenuated by uncoupling. Int J Biochem Cell Biol 40:2098–2109

    Article  PubMed  Google Scholar 

  19. Chan SH, Higgins E Jr (1978) Uncoupling activity of endogenous free fatty acids in rat liver mitochondria. Can J Biochem 56:111–116

    Article  CAS  PubMed  Google Scholar 

  20. Pfeiffer DR, Schmid PC, Beatrice MC, Schmid HH (1979) Intramitochondrial phospholipase activity and the effects of Ca2+ plus N-ethylmaleimide on mitochondrial function. J Biol Chem 254:11485–11494

    CAS  PubMed  Google Scholar 

  21. Birkett DJ, Myers SP, Sudlow G (1978) The fatty acid content and drug binding characteristics of commercial albumin preparations. Clin Chim Acta 85:253–258

    Article  CAS  PubMed  Google Scholar 

  22. Bonney RC, Qizilbash ST, Franks S (1988) Inhibition of phospholipase A2 isoenzymes in human endometrium by mefenamic acid and indomethacin: modulation by calcium ions. J Endocrinol 119:141–145. doi:10.1677/joe.0.1190141

    Article  CAS  PubMed  Google Scholar 

  23. Ghosh M, Loper R, Gelb MH, Leslie CC (2006) Identification of the expressed form of human cytosolic phospholipase A2beta (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early endosomes. J Biol Chem 281:16615–16624. doi:10.1074/jbc.M601770200

    Article  CAS  PubMed  Google Scholar 

  24. Tucker DE, Stewart A, Nallan L, Bendale P, Ghomashchi F, Gelb MH, Leslie CC (2005) Group IVC cytosolic phospholipase A2γ is farnesylated and palmitoylated in mammalian cells. J Lipid Res 46:2122–2133. doi:10.1194/jlr.M500230-JLR200

    Article  CAS  PubMed  Google Scholar 

  25. Kinsey GR, McHowat J, Patrick KS, Schnellmann RG (2007) Role of Ca2+-independent phospholipase A2γ in Ca2+-induced mitochondrial permeability transition. J Pharmacol Exp Ther 321:707–715. doi:10.1124/jpet107.119545

    Article  CAS  PubMed  Google Scholar 

  26. Williams SD, Gottlieb RA (2002) Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2) attenuates mitochondrial phospholipid loss and is cardioprotective. Biochem J 362:23–32

    Article  CAS  PubMed  Google Scholar 

  27. Nishihara Y, Utsumi K (1987) 4-Chloro-4′-biphenylol as an uncoupler and an inhibitor of mitochondrial oxidative phosphorylation. Biochem Pharmacol 36:3453–3457

    Article  CAS  PubMed  Google Scholar 

Download references


This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (C-#2100700).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Hiromi Yano.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yano, H., Oyanagi, E., Kato, Y. et al. l-Carnitine is essential to β-oxidation of quarried fatty acid from mitochondrial membrane by PLA2. Mol Cell Biochem 342, 95–100 (2010).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Oxygen consumption
  • ADP
  • CoA
  • β-oxidation
  • Fatty acid
  • Rat liver