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Impact of high dietary lipid intake and related metabolic disorders on the abundance and acyl composition of the unique mitochondrial phospholipid, cardiolipin

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Abstract

Excessive dietary lipid intake, coupled with lack of exercise, are the major causes of the development and progression of metabolic syndrome features e. g. obesity, hepatic steatosis, insulin resistance, type 2 diabetes and cardiovascular diseases. These metabolic diseases are associated with both structural and functional alterations of mitochondria. Cardiolipin (CL) is a unique phospholipid that is almost exclusively localized in the mitochondrial inner membrane. Cardiolipin is at the heart of mitochondrial metabolism playing a key role in several processes of mitochondrial bioenergetics as well as in mitochondrial membrane stability and dynamics, and in many of the mitochondrial-dependent steps of apoptosis. Indeed, alterations to CL content and acyl chain profile have been associated with mitochondrial dysfunction in multiple tissues in Barth syndrome and in many other physio-pathological conditions. After a brief overview of the biological roles of CL, we highlight the consequences of lipid overload-related nutritional manipulations as well as related metabolic disorders on both CL content and its fatty acid composition in the major metabolic tissues, the heart, muscle and liver. The goal of this review is to fill a void in the CL literature concerning the effects of CL abundance and form that arise following high lipid supplementation and the related metabolic disorders.

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Abbreviations

ANT:

Adenine nucleotide transporter

CDP-DAG:

Cytidine diphosphate-diacylglycerol

CDS:

CDP-DAG synthase

CL:

Cardiolipin

FA:

Fatty acid

ESI-MS:

Electrospray ionization mass spectrometry

GC:

Gas chromatography

G3P:

Glycerol-3-phosphate

HPLC:

High-performance liquid chromatography

MLCL:

Monolyso-CL

MLCL-AT:

MLCL-acyltransferase

MUFA:

Monounsaturated fatty acid

PA:

Phosphatidic acid

PGP:

Phosphatidylglycerolphosphate

PUFA:

Polyunsaturated fatty acid

ROS:

Reactive oxygen species

SFA:

Saturated fatty acid

TLC:

Thin-layer chromatography.

References

  • Acin-Perez R, Fernandez-Silva P, Peleato ML, Perez-Martos A, Enriquez JA (2008) Respiratory active mitochondrial supercomplexes. Mol Cell 32(4):529–539

    Article  CAS  Google Scholar 

  • Ahmed KA, Sawa T, Ihara H, Kasamatsu S, Yoshitake J, Rahaman MM et al (2012) Regulation by mitochondrial superoxide and NADPH oxidase of cellular formation of nitrated cyclic GMP: potential implications for ROS signalling. Biochem J 441(2):719–73

    Article  CAS  Google Scholar 

  • Aoun M, Fouret G, Michel F, Bonafos B, Ramos J, Cristol JP et al (2012a) Dietary fatty acids modulate liver mitochondrial cardiolipin content and its fatty acid composition in rats with non alcoholic fatty liver disease. J Bioenerg Biomembr 44(4):439–452

    Article  CAS  Google Scholar 

  • Aoun M, Feillet-Coudray C, Fouret G, Chabi B, Crouzier D, Ferreri C et al (2012b) Rat liver mitochondrial membrane characteristics and mitochondrial functions are more profoundly altered by dietary lipid quantity than by dietary lipid quality: effect of different nutritional lipid patterns. Br J Nutr 107(5):647–659

    Article  CAS  Google Scholar 

  • Baile MG, Sathappa M, Lu YW, Pryce E, Whited K, McCaffery JM et al (2014) Unremodeled and remodeled cardiolipin are functionally indistinguishable in yeast. J Biol Chem 289(3):1768–1778

    Article  CAS  Google Scholar 

  • Berg K, Ericsson M, Lindgren M, Gustafsson H (2014) A high precision method for quantitative measurements of reactive oxygen species in frozen biopsies. PLoS One 9(3):e90964

    Article  Google Scholar 

  • Blomstrand R, Svensson L (1975) Observations on lipid composition with particular reference to cardiolipin of rat heart after feeding rapeseed oil. Acta Med Scand Suppl 585:51–73

    CAS  Google Scholar 

  • Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292(1):C33–44

    Article  CAS  Google Scholar 

  • Chicco AJ, Sparagna GC, McCune SA, Johnson CA, Murphy RC, Bolden DA et al (2008) Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets. Hypertension 52(3):549–555

    Article  CAS  Google Scholar 

  • Claypool SM (2009) Cardiolipin, a critical determinant of mitochondrial carrier protein assembly and function. Biochim Biophys Acta 1788(10):2059–2068

    Article  CAS  Google Scholar 

  • Croston TL, Shepherd DL, Thapa D, Nichols CE, Lewis SE, Dabkowski ER et al (2013) Evaluation of the cardiolipin biosynthetic pathway and its interactions in the diabetic heart. Life Sci 93(8):313–322

    Article  CAS  Google Scholar 

  • Dabkowski ER, Williamson CL, Bukowski VC, Chapman RS, Leonard SS, Peer CJ et al (2009) Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations. Am J Physiol Heart Circ Physiol 296(2):H359–369

    Article  CAS  Google Scholar 

  • Dorn GW 2nd, Scorrano L (2010) Two close, too close: sarcoplasmic reticulum-mitochondrial crosstalk and cardiomyocyte fate. Circ Res 107(6):689–699

    Article  CAS  Google Scholar 

  • Dulloo AG, Montani JP (2012) Body composition, inflammation and thermogenesis in pathways to obesity and the metabolic syndrome: an overview. Obes Rev 13(Suppl 2):1–5

    Article  Google Scholar 

  • Eble KS, Coleman WB, Hantgan RR, Cunningham CC (1990) Tightly associated cardiolipin in the bovine heart mitochondrial ATP synthase as analyzed by 31P nuclear magnetic resonance spectroscopy. J Biol Chem 265(32):19434–19440

    CAS  Google Scholar 

  • Feillet-Coudray C, Aoun M, Fouret G, Bonafos B, Ramos J, Casas F et al (2013) Effects of long-term administration of saturated and n-3 fatty acid-rich diets on lipid utilisation and oxidative stress in rat liver and muscle tissues. Br J Nutr 110(10):1789–1802

    Article  CAS  Google Scholar 

  • Ferreira FM, Seica R, Oliveira PJ, Coxito PM, Moreno AJ, Palmeira CM et al (2003) Diabetes induces metabolic adaptations in rat liver mitochondria: role of coenzyme Q and cardiolipin contents. Biochim Biophys Acta 1639(2):113–120

    Article  CAS  Google Scholar 

  • Ferreira R, Guerra G, Padrao AI, Melo T, Vitorino R, Duarte JA et al (2013) Lipidomic characterization of streptozotocin-induced heart mitochondrial dysfunction. Mitochondrion 13(6):762–771

    Article  CAS  Google Scholar 

  • Giudetti AM, Sabetta S, di Summa R, Leo M, Damiano F, Siculella L et al (2003) Differential effects of coconut oil- and fish oil-enriched diets on tricarboxylate carrier in rat liver mitochondria. J Lipid Res 44(11):2135–2141

    Article  CAS  Google Scholar 

  • Gohil VM, Gvozdenovic-Jeremic J, Schlame M, Greenberg ML (2005) Binding of 10-N-nonyl acridine orange to cardiolipin-deficient yeast cells: implications for assay of cardiolipin. Anal Biochem 343(2):350–352

    Article  CAS  Google Scholar 

  • Gudbjarnason S, El-Hage AN, Whitehurst VE, Simental F, Balazs T (1987) Reduced arachidonic acid levels in major phospholipids of heart muscle in the diabetic rat. J Mol Cell Cardiol 19(11):1141–1146

    Article  CAS  Google Scholar 

  • Haines TH, Dencher NA (2002) Cardiolipin: a proton trap for oxidative phosphorylation. FEBS Lett 528(1–3):35–39

    Article  CAS  Google Scholar 

  • Han X, Yang J, Cheng H, Yang K, Abendschein DR, Gross RW (2005) Shotgun lipidomics identifies cardiolipin depletion in diabetic myocardium linking altered substrate utilization with mitochondrial dysfunction. Biochemistry 44(50):16684–16694

    Article  CAS  Google Scholar 

  • Han X, Yang J, Yang K, Zhao Z, Abendschein DR, Gross RW (2007) Alterations in myocardial cardiolipin content and composition occur at the very earliest stages of diabetes: a shotgun lipidomics study. Biochemistry 46(21):6417–6428

    Article  CAS  Google Scholar 

  • Hatch GM, Cao SG, Angel A (1995) Decrease in cardiac phosphatidylglycerol in streptozotocin-induced diabetic rats does not affect cardiolipin biosynthesis: evidence for distinct pools of phosphatidylglycerol in the heart. Biochem J 306(Pt 3):759–764

    CAS  Google Scholar 

  • Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069

    Article  CAS  Google Scholar 

  • He Q, Han X (2014) Cardiolipin remodeling in diabetic heart. Chem Phys Lipids 179:75–81

    Article  CAS  Google Scholar 

  • Hoch FL (1992) Cardiolipins and biomembrane function. Biochim Biophys Acta 1113(1):71–133

    Article  CAS  Google Scholar 

  • Horvath SE, Daum G (2013) Lipids of mitochondria. Prog Lipid Res 52(4):590–614

    Article  CAS  Google Scholar 

  • Houtkooper RH, Vaz FM (2008) Cardiolipin, the heart of mitochondrial metabolism. Cell Mol Life Sci 65(16):2493–2506

    Article  CAS  Google Scholar 

  • Khairallah RJ, Kim J, O’Shea KM, O’Connell KA, Brown BH, Galvao T et al (2012) Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids. PLoS One 7(3):e34402

    Article  CAS  Google Scholar 

  • Kim JA, Wei Y, Sowers JR (2008) Role of mitochondrial dysfunction in insulin resistance. Circ Res 102(4):401–414

    Article  CAS  Google Scholar 

  • Klingenberg M (2009) Cardiolipin and mitochondrial carriers. Biochim Biophys Acta 1788(10):2048–2058

    Article  CAS  Google Scholar 

  • Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y et al (2010) Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab 12(2):154–165

    Article  CAS  Google Scholar 

  • Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387

    Article  CAS  Google Scholar 

  • Ma ZA (2012) The role of peroxidation of mitochondrial membrane phospholipids in pancreatic beta -cell failure. Curr Diabetes Rev 8(1):69–75

    Article  CAS  Google Scholar 

  • Ma ZA, Zhao Z, Turk J (2012) Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus. Exp Diabetes Res 2012:703538

    Article  Google Scholar 

  • Maranzana E, Barbero G, Falasca AI, Lenaz G, Genova ML (2013) Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid Redox Signal 19(13):1469–1480

    Article  CAS  Google Scholar 

  • McMillen IC, Rattanatray L, Duffield JA, Morrison JL, MacLaughlin SM, Gentili S et al (2009) The early origins of later obesity: pathways and mechanisms. Adv Exp Med Biol 646:71–81

    Article  Google Scholar 

  • McMillin JB, Bick RJ, Benedict CR (1992) Influence of dietary fish oil on mitochondrial function and response to ischemia. Am J Physiol 263(5 Pt 2):H1479–1485

    CAS  Google Scholar 

  • Mejia EM, Nguyen H, Hatch GM (2014) Mammalian cardiolipin biosynthesis. Chem Phys Lipids 179:11–16

    Article  CAS  Google Scholar 

  • Miquel E, Cassina A, Martinez-Palma L, Souza JM, Bolatto C, Rodriguez-Bottero S et al (2014) Neuroprotective effects of the mitochondria-targeted antioxidant MitoQ in a model of inherited amyotrophic lateral sclerosis. Free Radic Biol Med 70:204–213

    Article  CAS  Google Scholar 

  • Monteiro JP, Pereira CV, Silva AM, Maciel E, Baldeiras I, Peixoto F et al (2013) Rapeseed oil-rich diet alters hepatic mitochondrial membrane lipid composition and disrupts bioenergetics. Arch Toxicol 87(12):2151–2163

    Article  CAS  Google Scholar 

  • Mulligan CM, Sparagna GC, Le CH, De Mooy AB, Routh MA, Holmes MG et al (2012) Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart. Cardiovasc Res 94(3):460–468

    Article  CAS  Google Scholar 

  • Osman C, Voelker DR, Langer T (2011) Making heads or tails of phospholipids in mitochondria. J Cell Biol 192(1):7–16

    Article  CAS  Google Scholar 

  • Pan HJ, Lin Y, Chen YE, Vance DE, Leiter EH (2006) Adverse hepatic and cardiac responses to rosiglitazone in a new mouse model of type 2 diabetes: relation to dysregulated phosphatidylcholine metabolism. Vascul Pharmacol 45(1):65–71

    Article  CAS  Google Scholar 

  • Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2010) Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med 48(10):1286–1295

    Article  CAS  Google Scholar 

  • Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2014a) Cardiolipin and mitochondrial function in health and disease. Antioxid Redox Signal 20(12):1925–1953

    Article  CAS  Google Scholar 

  • Paradies G, Paradies V, De Benedictis V, Ruggiero FM, Petrosillo G (2014b) Functional role of cardiolipin in mitochondrial bioenergetics. Biochim Biophys Acta 1837(4):408–417

    Article  CAS  Google Scholar 

  • Pepe S, Tsuchiya N, Lakatta EG, Hansford RG (1999) PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. Am J Physiol 276(1 Pt 2):H149–158

    CAS  Google Scholar 

  • Pessayre D, Fromenty B, Mansouri A (2004) Mitochondrial injury in steatohepatitis. Eur J Gastroenterol Hepatol 16(11):1095–1105

    Article  CAS  Google Scholar 

  • Petrosillo G, Portincasa P, Grattagliano I, Casanova G, Matera M, Ruggiero FM et al (2007) Mitochondrial dysfunction in rat with nonalcoholic fatty liver involvement of complex I, reactive oxygen species and cardiolipin. Biochim Biophys Acta 1767(10):1260–1267

    Article  CAS  Google Scholar 

  • Pope S, Land JM, Heales SJ (2008) Oxidative stress and mitochondrial dysfunction in neurodegeneration; cardiolipin a critical target? Biochim Biophys Acta 1777(7–8):794–799

    Article  CAS  Google Scholar 

  • Power GW, Yaqoob P, Harvey DJ, Newsholme EA, Calder PC (1994) The effect of dietary lipid manipulation on hepatic mitochondrial phospholipid fatty acid composition and carnitine palmitoyltransferase I activity. Biochem Mol Biol Int 34(4):671–684

    CAS  Google Scholar 

  • Ren M, Phoon CK, Schlame M (2014) Metabolism and function of mitochondrial cardiolipin. Prog Lipid Res 55C:1–16

    Article  Google Scholar 

  • Robblee NM, Clandinin MT (1984) Effect of dietary fat level and polyunsaturated fatty acid content on the phospholipid composition of rat cardiac mitochondrial membranes and mitochondrial ATPase activity. J Nutr 114(2):263–269

    CAS  Google Scholar 

  • Ruiz-Gutierrez V, Molina MT, Vazquez CM (1990) Comparative effects of feeding different fats on fatty acid composition of major individual phospholipids of rat hearts. Ann Nutr Metab 34(6):350–358

    Article  CAS  Google Scholar 

  • Schlame M (2008) Cardiolipin synthesis for the assembly of bacterial and mitochondrial membranes. J Lipid Res 49(8):1607–1620

    Article  CAS  Google Scholar 

  • Schlame M (2013) Cardiolipin remodeling and the function of tafazzin. Biochim Biophys Acta 1831(3):582–588

    Article  CAS  Google Scholar 

  • Schlame M, Ren M (2009) The role of cardiolipin in the structural organization of mitochondrial membranes. Biochim Biophys Acta 1788(10):2080–2083

    Article  CAS  Google Scholar 

  • Schlame M, Shanske S, Doty S, Konig T, Sculco T, DiMauro S et al (1999) Microanalysis of cardiolipin in small biopsies including skeletal muscle from patients with mitochondrial disease. J Lipid Res 40(9):1585–1592

    CAS  Google Scholar 

  • Schlame M, Rua D, Greenberg ML (2000) The biosynthesis and functional role of cardiolipin. Prog Lipid Res 39(3):257–288

    Article  CAS  Google Scholar 

  • Schlame M, Ren M, Xu Y, Greenberg ML, Haller I (2005) Molecular symmetry in mitochondrial cardiolipins. Chem Phys Lipids 138(1–2)

  • Schwall CT, Greenwood VL, Alder NN (2012) The stability and activity of respiratory complex II is cardiolipin-dependent. Biochim Biophys Acta 1817(9):1588–1596

    Article  CAS  Google Scholar 

  • Shi Y (2010) Emerging roles of cardiolipin remodeling in mitochondrial dysfunction associated with diabetes, obesity, and cardiovascular diseases. J Biomed Res 24(1):6–15

    Article  CAS  Google Scholar 

  • Simoes C, Domingues P, Ferreira R, Amado F, Duarte JA, Vitorino R et al (2013) Remodeling of liver phospholipidomic profile in streptozotocin-induced diabetic rats. Arch Biochem Biophys 538(2):95–102

    Article  CAS  Google Scholar 

  • Sparagna GC, Lesnefsky EJ (2009) Cardiolipin remodeling in the heart. J Cardiovasc Pharmacol 53(4):290–301

    Article  CAS  Google Scholar 

  • Stavrovskaya IG, Bird SS, Marur VR, Sniatynski MJ, Baranov SV, Greenberg HK et al (2013) Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins. J Lipid Res 54(10):2623–2635

    Article  CAS  Google Scholar 

  • Stefanyk LE, Coverdale N, Roy BD, Peters SJ, LeBlanc PJ (2010) Skeletal muscle type comparison of subsarcolemmal mitochondrial membrane phospholipid fatty acid composition in rat. J Membr Biol 234(3):207–215

    Article  CAS  Google Scholar 

  • Swanson JE, Kinsella JE (1986) Dietary n-3 polyunsaturated fatty acids: modification of rat cardiac lipids and fatty acid composition. J Nutr 116(4):514–523

    CAS  Google Scholar 

  • Tamura Y, Harada Y, Nishikawa S, Yamano K, Kamiya M, Shiota T et al (2013) Tam41 is a CDP-diacylglycerol synthase required for cardiolipin biosynthesis in mitochondria. Cell Metab 17(5):709–718

    Article  CAS  Google Scholar 

  • Taylor WA, Xu FY, Ma BJ, Mutter TC, Dolinsky VW, Hatch GM (2002) Expression of monolysocardiolipin acyltransferase activity is regulated in concert with the level of cardiolipin and cardiolipin biosynthesis in the mammalian heart. BMC Biochem 3:9

    Article  Google Scholar 

  • Tsalouhidou S, Argyrou C, Theofilidis G, Karaoglanidis D, Orfanidou E, Nikolaidis MG et al (2006) Mitochondrial phospholipids of rat skeletal muscle are less polyunsaturated than whole tissue phospholipids: implications for protection against oxidative stress. J Anim Sci 84(10):2818–2825

    Article  CAS  Google Scholar 

  • Wang HY, Jackson SN, Woods AS (2007) Direct MALDI-MS analysis of cardiolipin from rat organs sections. J Am Soc Mass Spectrom 18(3):567–577

    Article  CAS  Google Scholar 

  • Watkins SM, Lin TY, Davis RM, Ching JR, DePeters EJ, Halpern GM et al (2001) Unique phospholipid metabolism in mouse heart in response to dietary docosahexaenoic or alpha-linolenic acids. Lipids 36(3):247–254

    Article  CAS  Google Scholar 

  • Wolff RL, Entressangles B (1991) Compositional changes of fatty acids in the 1(1″)-and 2(2″)-positions of cardiolipin from liver, heart, and kidney mitochondria of rats fed a low-fat diet. Biochim Biophys Acta 1082(2):136–142

    Article  CAS  Google Scholar 

  • Yabuuchi H, O’Brien JS (1968) Brain cardiolipin: isolation and fatty acid positions. J Neurochem 15(12):1383–1390

    Article  CAS  Google Scholar 

  • Yamaoka S, Urade R, Kito M (1988) Mitochondrial function in rats is affected by modification of membrane phospholipids with dietary sardine oil. J Nutr 118(3):290–296

    CAS  Google Scholar 

  • Yamaoka S, Urade R, Kito M (1990) Cardiolipin molecular species in rat heart mitochondria are sensitive to essential fatty acid-deficient dietary lipids. J Nutr 120(5):415–421

    CAS  Google Scholar 

  • Ye C, Lou W, Li Y, Chatzispyrou IA, Huttemann M, Lee I et al (2014) Deletion of the cardiolipin-specific phospholipase Cld1 rescues growth and life span defects in the tafazzin mutant: implications for Barth syndrome. J Biol Chem 289(6)

  • Zhang M, Mileykovskaya E, Dowhan W (2005) Cardiolipin is essential for organization of complexes III and IV into a supercomplex in intact yeast mitochondria. J Biol Chem 280(33):29403–29408

    Article  CAS  Google Scholar 

  • Zhuravleva E, Gut H, Hynx D, Marcellin D, Bleck CK, Genoud C et al (2012) Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver development. Mol Cell Biol 32(14):2685–2697

    Article  CAS  Google Scholar 

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Acknowledgments

We declare that there are no conflicts of interest associated with this manuscript.

We would like to thank Dr Michael P. Murphy for critical reading of an earlier version of the manuscript and providing useful feed-back.

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  1. UMR 866, Dynamique Musculaire et Métabolisme, Centre INRA de Montpellier, 34060, Montpellier, France

    Christine Feillet-Coudray, Gilles Fouret, François Casas & Charles Coudray

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  1. Christine Feillet-Coudray
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  2. Gilles Fouret
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  3. François Casas
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  4. Charles Coudray
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Correspondence to Christine Feillet-Coudray.

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Feillet-Coudray, C., Fouret, G., Casas, F. et al. Impact of high dietary lipid intake and related metabolic disorders on the abundance and acyl composition of the unique mitochondrial phospholipid, cardiolipin. J Bioenerg Biomembr 46, 447–457 (2014). https://doi.org/10.1007/s10863-014-9555-y

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