The phospholipid environment of the mitochondrial inner membrane, which contains large amounts of cardiolipin, could play a key role in transport of the long chain fatty acids. In the present study, the pre-incubation of cardiolipin with the wild type carnitine palmitoyltransferase (CPT) II led to a more than 1.5-fold increase of enzyme activity at physiological temperatures. At higher temperatures, however, there was a pronounced loss of activity. The most frequent variant S113L showed even at 37 °C a great activity loss. Pre-incubation of the wild type with both malonyl-CoA and cardiolipin counteracted the positive effect of cardiolipin. Malonyl-CoA, however, showed no inhibition effect on the variant in presence of cardiolipin. The activity loss in presence of cardiolipin at fever simulating situations was more pronounced for the variant comparing to the wild type. The reason might be a disturbed membrane association or a blockage of the active center of the mutated enzyme.
CPT II deficiency Cardiolipin Membrane association Enzyme activity
carnitine / acylcarnitine translocase
gene coding for human muscle carnitine palmitoyltransferase II
inner mitochondrial membrane
outer mitochondrial membrane
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LMS, AT, MB & BM carried out the lab work and data analysis; LMS and SZ designed the study and drafted the manuscript. All authors gave final approval for publication.
This work was supported by the Deutsche Gesellschaft für Muskelkranke (DGM) e.V.
The authors declare that they have no conflict of interest.
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Garland Science, New YorkGoogle Scholar
Comte J, Maisterrena B, Gautheron DC (1976) Lipid composition and protein profiles of outer and inner membranes from pig heart mitochondria. Comparison with microsomes. Biochim Biophys Acta 419:271–284CrossRefGoogle Scholar
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 276:20182–20185CrossRefGoogle Scholar
Motlagh L, Golbik R, Sippl W, Zierz S (2016b) Stabilization of the thermolabile variant S113L of carnitine palmitoyltransferase II. Neurol Genet 2:e53CrossRefGoogle Scholar
Mynatt RL, Greenhaw JJ, Cook GA (1994) Cholate extracts of mitochondrial outer membranes increase inhibition by malonyl-CoA of carnitine palmitoyltransferase-I by a mechanism involving phospholipids. Biochem J 299(Pt 3):761–767CrossRefGoogle Scholar
Paradies G, Paradies V, De Benedictis V, Ruggiero FM, Petrosillo G (2014) Functional role of cardiolipin in mitochondrial bioenergetics. Biochim Biophys Acta 1837:408–417CrossRefGoogle Scholar
Planas-Iglesias J, Dwarakanath H, Mohammadyani D, Yanamala N, Kagan VE, Klein-Seetharaman J (2015) Cardiolipin interactions with proteins. Biophys J 109:1282–1294CrossRefGoogle Scholar
Schlame M, Haldar D (1993) Cardiolipin is synthesized on the matrix side of the inner membrane in rat liver mitochondria. J Biol Chem 268:74–79Google Scholar
Woeltje KF, Kuwajima M, Foster DW, McGarry JD (1987) Characterization of the mitochondrial carnitine palmitoyltransferase enzyme system. II. Use of detergents and antibodies. J Biol Chem 262:9822–9827Google Scholar
Woldegiorgis G, Bremer J, Shrago E (1985) Substrate inhibition of carnitine palmitoyltransferase by palmitoyl-CoA and activation by phospholipids and proteins. Biochim Biophys Acta 837:135–140CrossRefGoogle Scholar
Zierz S, Engel AG (1985) Regulatory properties of a mutant carnitine palmitoyltransferase in human skeletal muscle. Eur J Biochem 149:207–214CrossRefGoogle Scholar