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Open Access 01-04-2011 | Mitochondrial Medicine

Metabolic manipulators: a well founded strategy to combat mitochondrial dysfunction

Authors: Saskia Koene, Jan Smeitink

Published in: Journal of Inherited Metabolic Disease | Issue 2/2011

Abstract

Whilst the pathophysiology and genetics of mitochondrial disease are slowly being unraveled, currently no effective remedy for mitochondrial disorders is available. One particular strategy in mitochondrial medicine presently under study is metabolic manipulation. This approach is aimed at counteracting the deranged cell biological homeostasis caused by mitochondrial dysfunction, using dietary modifications or small molecule therapy. Cell biological alterations caused by mitochondrial dysfunction include increased reactive oxygen species production, enhanced lipid peroxidation and altered cellular calcium homeostasis. This review covers the five principles of metabolic manipulation: (1) prevention of oxidative damage by reactive oxygen species, (2) amelioration of lipid peroxidation, (3) correction of altered membrane potential, (4) restoration of calcium homeostasis, and (5) transcription regulation interference. We hypothesize that a combination of compounds targeting different metabolic pathways will abolish cellular disturbance arising as a consequences of mitochondrial dysfunction, and thereby improve or stabilize clinical features. However, only a handful of compounds have reached efficacy testing in mammals, and it remains unknown to what extent metabolic manipulation will affect the whole organism. Until a potent remedy is found, patients will remain dependent on supportive, not curative, interventions.

Adlam VJ, Harrison JC, Porteous CM et al (2005) Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J 19:1088–1095PubMed

Albano E, Cheeseman KH, Tomasi A et al (1986) Effect of spin traps in isolated rat hepatocytes and liver microsomes. Biochem Pharmacol 22: 3955–60.

Almeida L, Vaz-da-Silva M, Falcao A et al (2009) Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53(Suppl 1):S7–S15PubMed

Antonenko YN, Avetisyan AV, Bakeeva LE et al (2008) Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies. Biochemistry (Mosc) 73:1273–1287

Bach D, Pich S, Soriano FX et al (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278:17190–17197PubMed

Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120:483–495PubMed

Barak Y, Arnon S, Wolach B et al (1995) MELAS syndrome: peripheral neuropathy and cytochrome C-oxidase deficiency: a case report and review of the literature. Isr J Med Sci 31:224–229PubMed

Bastin J, Aubey F, Rotig A et al (2008) Activation of peroxisome proliferator-activated receptor pathway stimulates the mitochondrial respiratory chain and can correct deficiencies in patients’ cells lacking its components. J Clin Endocrinol Metab 93:1433–1441PubMed

Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506PubMed

Baur JA, Pearson KJ, Price NL et al (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342PubMed

Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4:517–529PubMed

Bhat KPL, Kosmeder JW 2nd, Pezzuto JM (2001) Biological effects of resveratrol. Antioxid Redox Signal 3:1041–1064PubMed

Biasutto L, Sassi N, Mattarei A et al (2009) Impact of mitochondriotropic quercetin derivatives on mitochondria. Biochim Biophys Acta (in press)

Bonnefont JP, Djouadi F, Prip-Buus C et al (2004) Carnitine palmitoyltransferases 1 and 2: biochemical, molecular and medical aspects. Mol Aspects Med 25:495–520PubMed

Bonnefont JP, Bastin J, Behin A et al (2009) Bezafibrate for an inborn mitochondrial beta-oxidation defect. N Engl J Med 360:838–840PubMed

Brini M, Pinton P, King MP et al (1999) A calcium signaling defect in the pathogenesis of a mitochondrial DNA inherited oxidative phosphorylation deficiency. Nat Med 5:951–954PubMed

Brown SE, Ross MF, Sanjuan-Pla A et al (2007) Targeting lipoic acid to mitochondria: synthesis and characterization of a triphenylphosphonium-conjugated alpha-lipoyl derivative. Free Radic Biol Med 42:1766–1780PubMed

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

Canto C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20:98–105PubMed

Chen RS, Huang CC, Chu NS (1997) Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. Eur Neurol 37:212–218PubMed

Chinnery P, Majamaa K, Turnbull D et al (2006) Treatment for mitochondrial disorders. Cochrane Database Syst Rev CD004426.

Corton JC, Brown-Borg HM (2005) Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. J Gerontol A Biol Sci Med Sci 60:1494–1509PubMed

Das S, Khan N, Mukherjee S et al (2008) Redox regulation of resveratrol-mediated switching of death signal into survival signal. Free Radic Biol Med 44:82–90PubMed

Davis LM, Rho JM, Sullivan PG (2008) UCP-mediated free fatty acid uncoupling of isolated cortical mitochondria from fasted animals: correlations to dietary modulations. Epilepsia 49(Suppl 8):117–119PubMed

Detmer SA, Chan DC (2007) Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol 8:870–879PubMed

Di Giovanni S, Mirabella M, Spinazzola A et al (2001) Coenzyme Q10 reverses pathological phenotype and reduces apoptosis in familial CoQ10 deficiency. Neurology 57:515–518PubMed

Di Prospero NA, Baker A, Jeffries N et al (2007) Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: a randomised, placebo-controlled trial. Lancet Neurol 6:878–886PubMed

DiMauro S, Schon EA (2008) Mitochondrial disorders in the nervous system. Annu Rev Neurosci 31:91–123PubMed

Distelmaier F, Koopman WJ, van den Heuvel LP et al (2009a) Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease. Brain 132:833–842PubMed

Distelmaier F, Visch HJ, Smeitink JA et al (2009b) The antioxidant Trolox restores mitochondrial membrane potential and Ca2+ -stimulated ATP production in human complex I deficiency. J Mol Med 87:515–522PubMed

Djouadi F, Aubey F, Schlemmer D et al (2005) Peroxisome proliferator activated receptor delta (PPARdelta) agonist but not PPARalpha corrects carnitine palmitoyl transferase 2 deficiency in human muscle cells PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity Sirt1 is involved in energy metabolism: the role of chronic ethanol feeding and resveratrol High absorption but very low bioavailability of oral resveratrol in humans Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. J Clin Endocrinol Metab 90:1791–1797PubMed

Duchowny MS (2005) Food for thought: the ketogenic diet and adverse effects in children. Epilepsy Curr 5:152–154PubMed

Esposti MD, Ngo A, Ghelli A et al (1996) The interaction of Q analogs, particularly hydroxydecyl benzoquinone (idebenone), with the respiratory complexes of heart mitochondria. Arch Biochem Biophys 330:395–400PubMed

Fato R, Bergamini C, Bortolus M et al (2009) Differential effects of mitochondrial Complex I inhibitors on production of reactive oxygen species. Biochim Biophys Acta 1787:384–392PubMed

Filipovska A, Kelso GF, Brown SE et al (2005) Synthesis and characterization of a triphenylphosphonium-conjugated peroxidase mimetic. Insights into the interaction of ebselen with mitochondria. J Biol Chem 280:24113–24126PubMed

Gresele P, Pignatelli P, Guglielmini G et al (2008) Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr 138:1602–1608PubMed

Hallows WC, Smith BC, Lee S et al (2009) Ure(k)a! Sirtuins regulate mitochondria. Cell 137:404–406PubMed

Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27:728–735PubMed

Hood DA (2001) Invited Review: contractile activity-induced mitochondrial biogenesis in skeletal muscle. J Appl Physiol 90:1137–1157PubMed

Horton KL, Stewart KM, Fonseca SB et al (2008) Mitochondria-penetrating peptides. Chem Biol 15:375–382PubMed

Houtkooper RH, Canto C, Wanders RJ et al (2009) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev (in press)

Hoye AT, Davoren JE, Wipf P et al (2008) Targeting mitochondria. Acc Chem Res 41:87–97PubMed

James AM, Cocheme HM, Smith RA et al (2005) Interactions of mitochondria-targeted and untargeted ubiquinones with the mitochondrial respiratory chain and reactive oxygen species. Implications for the use of exogenous ubiquinones as therapies and experimental tools. J Biol Chem 280:21295–21312PubMed

James AM, Sharpley MS, Manas AR et al (2007) Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases. J Biol Chem 282:14708–14718PubMed

Jarmuszkiewicz W, Navet R, Alberici LC et al (2004) Redox state of endogenous coenzyme q modulates the inhibition of linoleic acid-induced uncoupling by guanosine triphosphate in isolated skeletal muscle mitochondria. J Bioenerg Biomembr 36:493–502PubMed

Kang HC, Lee YM, Kim HD et al (2007) Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 48:82–88PubMed

Kelso GF, Porteous CM, Coulter CV et al (2001) Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem 276:4588–4596PubMed

Kode A, Rajendrasozhan S, Caito S et al (2008) Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 294:L478–L488PubMed

Koene S, Smeitink J (2009) Mitochondrial medicine: entering the era of treatment. J Intern Med 265:193–209PubMed

Koopman WJ, Verkaart S, Visch HJ et al (2005a) Inhibition of complex I of the electron transport chain causes O2-. -mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 288:C1440–C1450PubMed

Koopman WJ, Visch HJ, Verkaart S et al (2005b) Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency. Am J Physiol Cell Physiol 289:C881–C890PubMed

Koopman WJ, Verkaart S, Visch HJ et al (2007) Human NADH:ubiquinone oxidoreductase deficiency: radical changes in mitochondrial morphology? Am J Physiol Cell Physiol 293:C22–C29PubMed

Koopman WJ, Distelmaier F, Hink MA et al (2008a) Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria. Am J Physiol Cell Physiol 294:C1124–C1132PubMed

Koopman WJ, Verkaart S, van Emst-de Vries SE et al (2008b) Mitigation of NADH: ubiquinone oxidoreductase deficiency by chronic Trolox treatment. Biochim Biophys Acta 1777:853–859PubMed

Koopman WJ, Nijtmans LG, Dieteren CE et al (2009) Mammalian mitochondrial complex I: biogenesis, regulation and reactive oxygen species generation. Antioxid Redox Signal (in press)

Korzeniewski B (2007) Regulation of oxidative phosphorylation through parallel activation. Biophys Chem 129:93–110PubMed

Lash LH (2006) Mitochondrial glutathione transport: physiological, pathological and toxicological implications. Chem Biol Interact 163:54–67PubMed

Lehman JJ, Barger PM, Kovacs A et al (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106:847–856PubMed

Lenaz G, Genova ML (2009) Mobility and function of coenzyme Q (ubiquinone) in the mitochondrial respiratory chain. Biochim Biophys Acta 1787:563–573PubMed

Macias CA, Chiao JW, Xiao J et al (2007) Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock. Ann Surg 245:305–314PubMed

Magwere T, West M, Riyahi K et al (2006) The effects of exogenous antioxidants on lifespan and oxidative stress resistance in Drosophila melanogaster. Mech Ageing Dev 127:356–370PubMed

Man PY, Turnbull DM, Chinnery PF (2002) Leber hereditary optic neuropathy. J Med Genet 39:162–169PubMed

Mashima Y, Hiida Y, Oguchi Y (1992) Remission of Leber’s hereditary optic neuropathy with idebenone. Lancet 340:368–369PubMed

Mashima Y, Kigasawa K, Wakakura M et al (2000) Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy? J Neuroophthalmol 20:166–170PubMed

McGarry JD, Brown NF (1997) The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 244:1–14PubMed

Meier T, Buyse G (2009) Idebenone: an emerging therapy for Friedreich ataxia. J Neurol 256(Suppl 1):25–30PubMed

Milne JC, Denu JM (2008) The sirtuin family: therapeutic targets to treat diseases of aging. Curr Opin Chem Biol 12:11–17PubMed

Muratovska A, Lightowlers RN, Taylor RW et al (2001) Targeting large molecules to mitochondria. Adv Drug Deliv Rev 49:189–198PubMed

Murdock DG, Boone BE, Esposito LA et al (1999) Up-regulation of nuclear and mitochondrial genes in the skeletal muscle of mice lacking the heart/muscle isoform of the adenine nucleotide translocator. J Biol Chem 274:14429–14433PubMed

Murphy MP (2008) Targeting lipophilic cations to mitochondria. Biochim Biophys Acta 1777:1028–1031PubMed

Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13PubMed

Murphy MP, Smith RA (2007) Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol 47:629–656PubMed

Murphy MP, Echtay KS, Blaikie FH et al (2003) Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from alpha-phenyl-N-tert-butylnitrone. J Biol Chem 278:48534–48545PubMed

Neupert W (1997) Protein import into mitochondria. Annu Rev Biochem 66:863–917PubMed

Oliva J, French BA, Li J et al (2008) Sirt1 is involved in energy metabolism: the role of chronic ethanol feeding and resveratrol. Exp Mol Pathol 85:155–159PubMed

Pacholec M, Blasedale JE, Chrunyk B et al (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285:8340–8351PubMed

Pinton P, Giorgi C, Siviero R et al (2008) Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 27:6407–6418PubMed

Quinzii CM, DiMauro S, Hirano M (2007) Human coenzyme Q10 deficiency. Neurochem Res 32:723–727PubMed

Robb EL, Page MM, Wiens BE et al (2008) Molecular mechanisms of oxidative stress resistance induced by resveratrol: specific and progressive induction of MnSOD. Biochem Biophys Res Commun 367:406–412PubMed

Rodriguez-Cuenca S, Cocheme HM, Logan A et al (2010) Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free Radic Biol Med 48:161–172PubMed

Rossignol R, Gilkerson R, Aggeler R et al (2004) Energy substrate modulates mitochondrial structure and oxidative capacity in cancer cells. Cancer Res 64:985–993PubMed

Santra S, Gilkerson RW, Davidson M et al (2004) Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 56:662–669PubMed

Semenza GL (2004) O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. J Appl Physiol 96:1173–1177, discussion 1170-2PubMed

Sholtz KF, Solovjeva NA, Kotelnikova AV et al (1975) Effect of gramicidin S and its derivatives on the mitochondrial membrane. FEBS Lett 58:140–144PubMed

Skulachev VP (1998) Uncoupling: new approaches to an old problem of bioenergetics. Biochim Biophys Acta 1363:100–124PubMed

Skulachev VP (2009) Functions of mitochondria: from intracellular power stations to mediators of a senescence program. Cell Mol Life Sci 66:1785–1793PubMed

Skulachev VP, Anisimov VN, Antonenko YN et al (2009) An attempt to prevent senescence: a mitochondrial approach. Biochim Biophys Acta 1787:437–461PubMed

Sluse FE, Jarmuszkiewicz W, Navet R et al (2006) Mitochondrial UCPs: new insights into regulation and impact. Biochim Biophys Acta 1757:480–485PubMed

Smeitink JA, Zeviani M, Turnbull DM et al (2006) Mitochondrial medicine: a metabolic perspective on the pathology of oxidative phosphorylation disorders. Cell Metab 3:9–13PubMed

Smith RA, Porteous CM, Coulter CV et al (1999) Selective targeting of an antioxidant to mitochondria. Eur J Biochem 263:709–716PubMed

Smith RA, Adlam VJ, Blaikie FH et al (2008) Mitochondria-targeted antioxidants in the treatment of disease. Ann N Y Acad Sci 1147:105–111PubMed

St-Pierre J, Drori S, Uldry M et al (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408PubMed

Sullivan PG, Rippy NA, Dorenbos K et al (2004) The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 55:576–580PubMed

Szeto HH (2006a) Cell-permeable, mitochondrial-targeted, peptide antioxidants. AAPS J 8:E277–E283PubMed

Szeto HH (2006b) Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J 8:E521–E531PubMed

Tafazoli S, Wright JS, O’Brien PJ (2005) Prooxidant and antioxidant activity of vitamin E analogues and troglitazone. Chem Res Toxicol 18:1567–1574PubMed

Taivassalo T, Haller RG (2005) Exercise and training in mitochondrial myopathies. Med Sci Sports Exerc 37:2094–2101PubMed

Tavi P, Hansson A, Zhang SJ et al (2005) Abnormal Ca(2+) release and catecholamine-induced arrhythmias in mitochondrial cardiomyopathy. Hum Mol Genet 14:1069–1076PubMed

Toshima K, Kuroda Y, Hashimoto T et al (1982) Enzymologic studies and therapy of Leigh’s disease associated with pyruvate decarboxylase deficiency. Pediatr Res 16:430–435PubMed

Valsecchi F, Esseling JJ, Koopman WJ et al (2009) Calcium and ATP handling in human NADH:Ubiquinone oxidoreductase deficiency. Biochim Biophys Acta (in press)

Verkaart S, Koopman WJ, Cheek J et al (2007) Mitochondrial and cytosolic thiol redox state are not detectably altered in isolated human NADH:ubiquinone oxidoreductase deficiency. Biochim Biophys Acta 1772:1041–1051PubMed

Visch HJ, Rutter GA, Koopman WJ et al (2004) Inhibition of mitochondrial Na+-Ca2+ exchange restores agonist-induced ATP production and Ca2+ handling in human complex I deficiency. J Biol Chem 279:40328–40336PubMed

Visch HJ, Koopman WJ, Zeegers D et al (2006) Ca2+-mobilizing agonists increase mitochondrial ATP production to accelerate cytosolic Ca2+ removal: aberrations in human complex I deficiency. Am J Physiol Cell Physiol 291:C308–C316PubMed

Walle T, Hsieh F, DeLegge MH et al (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377–1382PubMed

Wang SB, Weng WC, Lee NC et al (2008) Mutation of mitochondrial DNA G13513A presenting with Leigh syndrome, Wolff-Parkinson-White syndrome and cardiomyopathy. Pediatr Neonatol 49:145–149PubMed

Wenz T (2009) PGC-1alpha activation as a therapeutic approach in mitochondrial disease. IUBMB Life 61:1051–1062PubMed

Wenz T, Diaz F, Spiegelman BM et al (2008) Activation of the PPAR/PGC-1alpha pathway prevents a bioenergetic deficit and effectively improves a mitochondrial myopathy phenotype. Cell Metab 8:249–256PubMed

Wexler ID, Hemalatha SG, McConnell J et al (1997) Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 49:1655–1661PubMed

Wijburg FA, Barth PG, Bindoff LA et al (1992) Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet. Neuropediatrics 23:147–152PubMed

Witschi A, Reddy S, Stofer B et al (1992) The systemic availability of oral glutathione. Eur J Clin Pharmacol 43:667–669PubMed

Yang L, Zhao K, Calingasan NY et al (2009) Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine neurotoxicity. Antioxid Redox Signal (in press)

Zhao K, Zhao GM, Wu D et al (2004) Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem 279:34682–34690PubMed

Title: Metabolic manipulators: a well founded strategy to combat mitochondrial dysfunction
Authors: Saskia Koene
Jan Smeitink
Publication date: 01-04-2011
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 2/2011
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-010-9162-y

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