Drugs for the Treatment of Mitochondrial Diseases

Author(s): Diego F. Gomez-Casati* , Maria V. Busi .

Journal Name: Current Chemical Biology

Volume 13 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Mitochondrial diseases are a complex group of pathologies caused by mutations in genes coded in the nuclear and/or the mitochondrial DNA, which fulfill their function in the organelle. The diagnosis is also complex, since it depends on the integration of biochemical, histological and imaging data.

Objective: In this paper we review the use of some of these substances and their efficacy in the treatment of these disorders.

Conclusions: Currently, there is not a fully effective treatment, however, it was demonstrated that the use of some vitamins, amino acids, antioxidants along with a proper diet and exercise have an important effect that leads to improve the overall state of patients with mitochondrial disorders.

Keywords: Mitochondria, diseases, reactive oxygen species, mitochondrial drugs, pharmacological approaches, vitamins, antioxidants.

Valenti D, Braidy N, De Rasmo D, et al. Mitochondria as pharmacological targets in down syndrome. Free Radic Biol Med 2018; 114: 69-83.
Von Kleist-Retzow JC, Schauseil-Zipf U, Michalk DV, Kunz WS. Mitochondrial diseases--an expanding spectrum of disorders and affected genes. Exp Physiol 2003; 88(1): 155-66.
Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R. Medicine Society TM: A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol 2009; 11(6): 414-30.
Rai PK, Russell OM, Lightowlers RN, Turnbull DM. Potential compounds for the treatment of mitochondrial disease. Br Med Bull 2015; 116: 5-18.
Kagan T, Davis C, Lin L, Zakeri Z. Coenzyme Q10 can in some circumstances block apoptosis, and this effect is mediated through mitochondria. Ann N Y Acad Sci 1999; 887: 31-47.
Trevisson E, DiMauro S, Navas P, Salviati L. Coenzyme Q deficiency in muscle. Curr Opin Neurol 2011; 24(5): 449-56.
Turunen M, Olsson J, Dallner G. Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004; 1660(1-2): 171-99.
Garrido-Maraver J, Cordero MD, Oropesa-Avila M, et al. Coenzyme q10 therapy. Mol Syndromol 2014; 5(3-4): 187-97.
Salviati L, Trevisson E, Doimo M, Navas P. Primary coenzyme Q10 deficiency.GeneReviews(R). Seattle: University of Washington 1993.
Sikorska M, Lanthier P, Miller H, et al. Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson’s disease. Neurobiol Aging 2014; 35(10): 2329-46.
Jing L, He MT, Chang Y, et al. Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway. Int J Biol Sci 2015; 11(1): 59-66.
Henriques BJ, Olsen RK, Bross P, Gomes CM. Emerging roles for riboflavin in functional rescue of mitochondrial beta-oxidation flavoenzymes. Curr Med Chem 2010; 17(32): 3842-54.
Udhayabanu T, Manole A, Rajeshwari M, Varalakshmi P, Houlden H, Ashokkumar B. Riboflavin responsive mitochondrial dysfunction in neurodegenerative diseases. J Clin Med 2017; 6(5): E52.
Xin Z, Pu L, Gao W, et al. Riboflavin deficiency induces a significant change in proteomic profiles in HepG2 cells. Sci Rep 2017; 7: 45861.
Huang YF, Liu SY, Yen CL, Yang PW, Shieh CC. Thapsigargin and flavin adenine dinucleotide ex vivo treatment rescues trafficking-defective gp91phox in chronic granulomatous disease leukocytes. Free Radic Biol Med 2009; 47(7): 932-40.
Abbas CA, Sibirny AA. Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers. Microbiol Mol Biol Rev 2011; 75(2): 321-60.
Gonzalez-Cabo P, Ros S, Palau F. Flavin adenine dinucleotide rescues the phenotype of frataxin deficiency. PLoS One 2010; 5: e8872.
Campuzano V, Montermini L, Molto MD, et al. Friedreich’s ataxia: Autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996; 271(5254): 1423-7.
Babcock M, de Silva D, Oaks R, et al. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 1997; 276(5319): 1709-12.
Busi MV, Gomez-Casati DF. Exploring frataxin function. IUBMB Life 2012; 64(1): 56-63.
Maliandi MV, Busi MV, Turowski VR, et al. The mitochondrial protein frataxin is essential for heme biosynthesis in plants. FEBS J 2011; 278(3): 470-81.
Ristow M, Pfister MF, Yee AJ, et al. Frataxin activates mitochondrial energy conversion and oxidative phosphorylation. Proc Natl Acad Sci USA 2000; 97(22): 12239-43.
Muhlenhoff U, Richhardt N, Ristow M, Kispal G, Lill R. The yeast frataxin homolog Yfh1p plays a specific role in the maturation of cellular Fe/S proteins. Hum Mol Genet 2002; 11(17): 2025-36.
Chen OS, Hemenway S, Kaplan J. Inhibition of Fe-S cluster biosynthesis decreases mitochondrial iron export: Evidence that Yfh1p affects Fe-S cluster synthesis. Proc Natl Acad Sci USA 2002; 99(19): 12321-6.
Spampinato CP, Gomez-Casati DF. Research on plants for the understanding of diseases of nuclear and mitochondrial origin. J Biomed Biotechnol 2012; 2012: 836196.
Massey V. The chemical and biological versatility of riboflavin. Biochem Soc Trans 2000; 28(4): 283-96.
Stewart VC, Heales SJ. Nitric oxide-induced mitochondrial dysfunction: Implications for neurodegeneration. Free Radic Biol Med 2003; 34(3): 287-303.
Rodan LH, Wells GD, Banks L, Thompson S, Schneiderman JE, Tein I. L-Arginine affects aerobic capacity and muscle metabolism in MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) syndrome. PLoS One 2015; 10: e0127066.
Nozuma S, Okamoto Y, Higuchi I, et al. Clinical and electron microscopic findings in two patients with mitochondrial myopathy associated with episodic hyper-creatine kinase-emia. Intern Med 2015; 54(24): 3209-14.
Koga Y, Povalko N, Nishioka J, Katayama K, Kakimoto N, Matsuishi T. MELAS and L-arginine therapy: Pathophysiology of stroke-like episodes. Ann N Y Acad Sci 2010; 1201: 104-10.
Szeto HH, Birk AV. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin Pharmacol Ther 2014; 96(6): 672-83.
Shi J, Dai W, Hale SL, et al. Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart. Life Sci 2015; 141: 170-8.
Gueven N, Nadikudi M, Daniel A, Chhetri J. Targeting mitochondrial function to treat optic neuropathy. Mitochondrion 2017; 36: 7-14.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [19 - 24]
Pages: 6
DOI: 10.2174/2212796812666180515122303
Price: $58

Article Metrics

PDF: 69