Understanding D-Ribose and Mitochondrial Function

Diane E. Mahoney, John B. Hiebert, Amanda Thimmesch, John T. Pierce, James L. Vacek, Richard L. Clancy, Andrew J. Sauer, Janet D. Pierce


Mitochondria are important organelles referred to as cellular powerhouses for their unique properties of cellular energy production.  With many pathologic conditions and aging, mitochondrial function declines, and there is a reduction in the production of adenosine triphosphate. The energy carrying molecule generated by cellular respiration and by pentose phosphate pathway, an alternative pathway of glucose metabolism. D-ribose is a naturally occurring monosaccharide found in the cells and particularly in the mitochondria is essential in energy production. Without sufficient energy, cells cannot maintain integrity and function. Supplemental D-ribose has been shown to improve cellular processes when there is mitochondrial dysfunction. When individuals take supplemental D-ribose, it can bypass part of the pentose pathway to produce D-ribose-5-phosphate for the production of energy. In this article, we review how energy is produced by cellular respiration, the pentose pathway, and the use of supplemental D-ribose.  


Adenosine triphosphate; Bioenergetics; D-ribose; Mitochondria

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Martin-Fernandez B,Gredilla R. Mitochondria and oxidative stress in heart aging. Age (Dordr). 2016;38:225-238. doi: 10.1007/s11357-016-9933-y.

Wallace DC, Fan W, Procaccio V. Mitochondrial energetics and therapeutics. Annu Rev Pathol. 2010;5:297-348. doi: 10.1146/annurev.pathol.4.110807.092314.

Schapira AH. Mitochondrial disease. Lancet. 2006;368:70-82. doi: 10.1016/S0140-6736(06)68970-8.

Nicolson GL. Mitochondrial Dysfunction and Chronic Disease: Treatment With Natural Supplements. Integr Med (Encinitas). 2014;13:35-43. doi:

Lesnefsky EJ, Chen Q, Hoppel CL. Mitochondrial Metabolism in Aging Heart. Circ Res. 2016;118:1593-1611. doi: 10.1161/CIRCRESAHA.116.307505.

Lane N. Energetics and genetics across the prokaryote-eukaryote divide. Biol Direct. 2011;6:35. doi: 10.1186/1745-6150-6-35.

Picard M, Wallace DC, Burelle Y. The rise of mitochondria in medicine. Mitochondrion. 2016;30:105-116. doi: 10.1016/j.mito.2016.07.003.

Chinnery PF,Hudson G. Mitochondrial genetics. Br Med Bull. 2013;106:135-159. doi: 10.1093/bmb/ldt017.

Pauly DF,Pepine CJ. D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000;5:249-258. doi: 10.1054/JCPT.2000.18011.

Herrick J,St Cyr J. Ribose in the heart. J Diet Suppl. 2008;5:213-217. doi: 10.1080/19390210802332752.

Leites EP,Morais VA. Mitochondrial quality control pathways: PINK1 acts as a gatekeeper. Biochem Biophys Res Commun. 2017;doi: 10.1016/j.bbrc.2017.06.096.

Ettema TJ. Evolution: Mitochondria in the second act. Nature. 2016;531:39-40. doi: 10.1038/nature16876.

Agrawal A,Mabalirajan U. Rejuvenating cellular respiration for optimizing respiratory function: targeting mitochondria. Am J Physiol Lung Cell Mol Physiol. 2016;310:L103-113. doi: 10.1152/ajplung.00320.2015.

Wei H, Liu L, Chen Q. Selective removal of mitochondria via mitophagy: distinct pathways for different mitochondrial stresses. Biochim Biophys Acta. 2015;1853:2784-2790. doi: 10.1016/j.bbamcr.2015.03.013.

Mills EL, Kelly B, O'Neill LAJ. Mitochondria are the powerhouses of immunity. Nat Immunol. 2017;18:488-498. doi: 10.1038/ni.3704.

Kim SJ, Xiao J, Wan J, Cohen P, Yen K. Mitochondrially derived peptides as novel regulators of metabolism. J Physiol. 2017;595:6613-6621. doi: 10.1113/JP274472.

de Almeida A, Ribeiro TP, de Medeiros IA. Aging: Molecular Pathways and Implications on the Cardiovascular System. Oxid Med Cell Longev. 2017;2017:7941563. doi: 10.1155/2017/7941563.

Feng D, Liu L, Zhu Y, Chen Q. Molecular signaling toward mitophagy and its physiological significance. Exp Cell Res. 2013;319:1697-1705. doi: 10.1016/j.yexcr.2013.03.034.

Polster BM, Carri MT, Beart PM. Mitochondria in the nervous system: From health to disease, Part I. Neurochem Int. 2017;109:1-4. doi: 10.1016/j.neuint.2017.09.006.

Liesa M,Shirihai OS. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 2013;17:491-506. doi: 10.1016/j.cmet.2013.03.002.

Gomes LC,Scorrano L. Mitochondrial morphology in mitophagy and macroautophagy. Biochim Biophys Acta. 2013;1833:205-212. doi: 10.1016/j.bbamcr.2012.02.012.

Tamura Y, Sesaki H, Endo T. Phospholipid transport via mitochondria. Traffic. 2014;15:933-945. doi: 10.1111/tra.12188.

Zhang Q, Tamura Y, Roy M, Adachi Y, Iijima M, Sesaki H. Biosynthesis and roles of phospholipids in mitochondrial fusion, division and mitophagy. Cell Mol Life Sci. 2014;71:3767-3778. doi: 10.1007/s00018-014-1648-6.

Meyer JN, Leuthner TC, Luz AL. Mitochondrial fusion, fission, and mitochondrial toxicity. Toxicology. 2017;391:42-53. doi: 10.1016/j.tox.2017.07.019.

Wasilewski M, Chojnacka K, Chacinska A. Protein trafficking at the crossroads to mitochondria. Biochim Biophys Acta. 2017;1864:125-137. doi: 10.1016/j.bbamcr.2016.10.019.

Neupert W. A perspective on transport of proteins into mitochondria: a myriad of open questions. J Mol Biol. 2015;427:1135-1158. doi: 10.1016/j.jmb.2015.02.001.

Martinez-Reyes I, Diebold LP, Kong H, Schieber M, Huang H, Hensley CT, Mehta MM, Wang T, et al. TCA Cycle and Mitochondrial Membrane Potential Are Necessary for Diverse Biological Functions. Mol Cell. 2016;61:199-209. doi: 10.1016/j.molcel.2015.12.002.

Donnelly RP,Finlay DK. Glucose, glycolysis and lymphocyte responses. Mol Immunol. 2015;68:513-519. doi: 10.1016/j.molimm.2015.07.034.

Lunt SY, Muralidhar V, Hosios AM, Israelsen WJ, Gui DY, Newhouse L, Ogrodzinski M, Hecht V, et al. Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation. Mol Cell. 2015;57:95-107. doi: 10.1016/j.molcel.2014.10.027.

Sutendra G, Kinnaird A, Dromparis P, Paulin R, Stenson TH, Haromy A, Hashimoto K, Zhang N, et al. A nuclear pyruvate dehydrogenase complex is important for the generation of acetyl-CoA and histone acetylation. Cell. 2014;158:84-97. doi: 10.1016/j.cell.2014.04.046.

Rieger B, Junge W, Busch KB. Lateral pH gradient between OXPHOS complex IV and F(0)F(1) ATP-synthase in folded mitochondrial membranes. Nat Commun. 2014;5:3103. doi: 10.1038/ncomms4103.

Kuhlbrandt W. Structure and function of mitochondrial membrane protein complexes. BMC Biol. 2015;13:89. doi: 10.1186/s12915-015-0201-x.

Matta CF,Massa L. Energy Equivalence of Information in the Mitochondrion and the Thermodynamic Efficiency of ATP Synthase. Biochemistry. 2015;54:5376-5378. doi: 10.1021/acs.biochem.5b00834.

Ghosh K, Debasis K, Purnendu R. Benzimidazolium-based simple host for fluorometric sensing of H2PO4-, F−, PO43- and AMP under different conditions. Tetrahedron Letters. 2011;52:5098-5103. doi: 10.1016/j.tetlet.2011.07.110.

Vyas NK, Vyas MN, Quiocho FA. Comparison of the periplasmic receptors for L-arabinose, D-glucose/D-galactose, and D-ribose. Structural and Functional Similarity. J Biol Chem. 1991;266:5226-5237. doi:

Wamelink MM, Struys EA, Jakobs C. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis. 2008;31:703-717. doi: 10.1007/s10545-008-1015-6.

Tanuma S, Sato A, Oyama T, Yoshimori A, Abe H, Uchiumi F. New Insights into the Roles of NAD+-Poly(ADP-ribose) Metabolism and Poly(ADP-ribose) Glycohydrolase. Curr Protein Pept Sci. 2016;17:668-682. doi:

Link H, Fuhrer T, Gerosa L, Zamboni N, Sauer U. Real-time metabolome profiling of the metabolic switch between starvation and growth. Nat Methods. 2015;12:1091-1097. doi: 10.1038/nmeth.3584.

Frenguelli BG. The Purine Salvage Pathway and the Restoration of Cerebral ATP: Implications for Brain Slice Physiology and Brain Injury. Neurochem Res. 2017;doi: 10.1007/s11064-017-2386-6.

Bayram M, St Cyr JA, Abraham WT. D-ribose aids heart failure patients with preserved ejection fraction and diastolic dysfunction: a pilot study. Ther Adv Cardiovasc Dis. 2015;9:56-65. doi: 10.1177/1753944715572752.

Jones K,Probst Y. Role of dietary modification in alleviating chronic fatigue syndrome symptoms: a systematic review. Aust N Z J Public Health. 2017;41:338-344. doi: 10.1111/1753-6405.12670.

Thompson J, Neutel J, Homer K, Tempero K, Shah A, Khankari R. Evaluation of D-ribose pharmacokinetics, dose proportionality, food effect, and pharmacodynamics after oral solution administration in healthy male and female subjects. J Clin Pharmacol. 2014;54:546-554. doi: 10.1002/jcph.241.

St Cyr JA, Bianco RW, Schneider JR, Mahoney JR, Jr., Tveter K, Einzig S, Foker JE. Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model. J Surg Res. 1989;46:157-162. doi:

Pliml W, von Arnim T, Stablein A, Hofmann H, Zimmer HG, Erdmann E. Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet. 1992;340:507-510. doi:

Wagner DR, Gresser U, Kamilli I, Gross M, Zollner N. Effects of oral ribose on muscle metabolism during bicycle ergometer in patients with AMP-deaminase-deficiency. Adv Exp Med Biol. 1991;309B:383-385. doi:

Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006;12:857-862. doi: 10.1089/acm.2006.12.857.

Seifert J, Frelich A, Shecterle L, St Cyr J. Assessment of Hematological and Biochemical parameters with extended D-Ribose ingestion. J Int Soc Sports Nutr. 2008;5:13. doi: 10.1186/1550-2783-5-13.

Pliml W, von Arnim T, Hammer C. Effects of therapeutic ribose levels on human lymphocyte proliferation in vitro. Clin Investig. 1993;71:770-773.

DOI: https://doi.org/10.7575/aiac.abcmed.v.6n.1p.1


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