Creatine as a mitochondrial theranostic in predictive, preventive, and personalized medicine

Golubnitschaja O, Kinkorova J, Costigliola V. Predictive, preventive and personalised medicine as the hardcore of ‘Horizon 2020’: EPMA position paper. EPMA J. 2014;5(1): 6. https://doi.org/10.1186/1878-5085-5-6.

Article  PubMed  PubMed Central  Google Scholar 

Koklesova L, Mazurakova A, Samec M, Kudela E, Biringer K, Kubatka P, Golubnitschaja O. Mitochondrial health quality control: measurements and interpretation in the framework of predictive, preventive, and personalized medicine. EPMA J. 2022;13(2):177–93. https://doi.org/10.1007/s13167-022-00281-6.

Article  PubMed  PubMed Central  Google Scholar 

Pesta M, Mrazova B, Kapalla M, Kulda V, Gkika E, Golubnitschaja O. Mitochondria-based holistic 3PM approach as the ‘game-changer’ for individualised rehabilitation-the proof-of-principle model by treated breast cancer survivors. EPMA J. 2024;15(4):559–71. https://doi.org/10.1007/s13167-024-00386-0.

Article  PubMed  PubMed Central  Google Scholar 

Shao Q, Ndzie Noah ML, Golubnitschaja O, Zhan X. Mitochondrial medicine: “from bench to bedside” 3PM-guided concept. EPMA J. 2025;16(2):239–64. https://doi.org/10.1007/s13167-025-00409-4.

Article  PubMed  PubMed Central  Google Scholar 

Pajares S, Arias A, García-Villoria J, Briones P, Ribes A. Role of creatine as biomarker of mitochondrial diseases. Mol Genet Metab. 2013;108(2):119–24. https://doi.org/10.1016/j.ymgme.2012.11.283.

Article  CAS  PubMed  Google Scholar 

Ostojic SM. Plasma creatine as a marker of mitochondrial dysfunction. Med Hypotheses. 2018;113:52–3. https://doi.org/10.1016/j.mehy.2018.02.022.

Article  CAS  PubMed  Google Scholar 

Kamel MA, Moussa YY, Gowayed MA. Creatine monohydrate for mitochondrial nutrition. In: Ostojic SM, editors. Molecular Nutrition and Mitochondria. Academic Press; 2023. pp. 383–415. https://doi.org/10.1016/B978-0-323-90256-4.00004-7

Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids. 2011;40(5):1271–96. https://doi.org/10.1007/s00726-011-0877-3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gutiérrez-Hellín J, Del Coso J, Franco-Andrés A, Gamonales JM, Espada MC, González-García J, López-Moreno M, Varillas-Delgado D. Creatine supplementation beyond athletics: benefits of different types of creatine for women, vegans, and clinical populations-a narrative review. Nutrients. 2024;17(1): 95. https://doi.org/10.3390/nu17010095.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sahlin K, Harris RC. The creatine kinase reaction: a simple reaction with functional complexity. Amino Acids. 2011;40(5):1363–7. https://doi.org/10.1007/s00726-011-0856-8.

Article  CAS  PubMed  Google Scholar 

Karo J, Peterson P, Vendelin M. Molecular dynamics simulations of creatine kinase and adenine nucleotide translocase in mitochondrial membrane patch. J Biol Chem. 2012;287(10):7467–76. https://doi.org/10.1074/jbc.M111.332320.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ostojic SM. Impaired bioenergetics in clinical medicine: a target to tackle. Tohoku J Exp Med. 2017;243(4):227–35. https://doi.org/10.1620/tjem.243.227.

Article  PubMed  Google Scholar 

Lygate CA, Medway DJ, Ostrowski PJ, Aksentijevic D, Sebag-Montefiore L, Hunyor I, Zervou S, Schneider JE, Neubauer S. Chronic creatine kinase deficiency eventually leads to congestive heart failure, but severity is dependent on genetic background, gender and age. Basic Res Cardiol. 2012;107(5):276. https://doi.org/10.1007/s00395-012-0276-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fons C, Campistol J. Creatine defects and central nervous system. Semin Pediatr Neurol. 2016;23(4):285–9. https://doi.org/10.1016/j.spen.2016.11.003.

Article  PubMed  Google Scholar 

Ghirardini E, Calugi F, Sagona G, Di Vetta F, Palma M, Battini R, Cioni G, Pizzorusso T, Baroncelli L. The role of preclinical models in creatine transporter deficiency: neurobiological mechanisms, biomarkers and therapeutic development. Genes (Basel). 2021;12(8): 1123. https://doi.org/10.3390/genes12081123.

Article  CAS  PubMed  Google Scholar 

Ranisavljev M, Todorovic N, Ostojic J, Ostojic SM. Reduced tissue creatine levels in patients with long COVID-19: A cross-sectional study. J Postgrad Med. 2023;69(3):162–3. https://doi.org/10.4103/jpgm.jpgm_65_23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maniti O, Lecompte MF, Marcillat O, Vial C, Granjon T. Mitochondrial creatine kinase interaction with cardiolipin-containing biomimetic membranes is a two-step process involving adsorption and insertion. Eur Biophys J. 2010;39(12):1649–55. https://doi.org/10.1007/s00249-010-0600-4.

Article  CAS  PubMed  Google Scholar 

Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Role of cardiolipin in mitochondrial function and dynamics in health and disease: molecular and pharmacological aspects. Cells. 2019;8(7): 728. https://doi.org/10.3390/cells8070728.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dolder M, Wendt S, Wallimann T. Mitochondrial creatine kinase in contact sites: interaction with porin and adenine nucleotide translocase, role in permeability transition and sensitivity to oxidative damage. Biol Signals Recept. 2001;10(1–2):93–111. https://doi.org/10.1159/000046878.

Article  CAS  PubMed  Google Scholar 

Brosnan ME, Edison EE, da Silva R, Brosnan JT. New insights into creatine function and synthesis. Adv Enzyme Regul. 2007;47:252–60. https://doi.org/10.1016/j.advenzreg.2006.12.005.

Article  CAS  PubMed  Google Scholar 

Schlattner U, Tokarska-Schlattner M, Wallimann T. Mitochondrial creatine kinase in human health and disease. Biochim Biophys Acta. 2006;1762(2):164–80. https://doi.org/10.1016/j.bbadis.2005.09.004.

Article  CAS  PubMed  Google Scholar 

Whittington HJ, Ostrowski PJ, McAndrew DJ, Cao F, Shaw A, Eykyn TR, Lake HA, Tyler J, Schneider JE, Neubauer S, Zervou S, Lygate CA. Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion. Cardiovasc Res. 2018;114(6):858–69. https://doi.org/10.1093/cvr/cvy054.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barbieri E, Guescini M, Calcabrini C, Vallorani L, Diaz AR, Fimognari C, Canonico B, Luchetti F, Papa S, Battistelli M, Falcieri E, Romanello V, Sandri M, Stocchi V, Ciacci C, Sestili P. Creatine prevents the structural and functional damage to mitochondria in myogenic, oxidatively stressed C2C12 cells and restores their differentiation capacity. Oxid Med Cell Longev. 2016;2016: 5152029. https://doi.org/10.1155/2016/5152029.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Taskin S, Celik T, Demiryurek S, Turedi S, Taskin A. Effects of different-intensity exercise and creatine supplementation on mitochondrial biogenesis and redox status in mice. Iran J Basic Med Sci. 2022;25(8):1009–15. https://doi.org/10.22038/IJBMS.2022.65047.14321.

Article  PubMed  PubMed Central  Google Scholar 

Berneburg M, Gremmel T, Kürten V, Schroeder P, Hertel I, von Mikecz A, Wild S, Chen M, Declercq L, Matsui M, Ruzicka T, Krutmann J. Creatine supplementation normalizes mutagenesis of mitochondrial DNA as well as functional consequences. J Invest Dermatol. 2005;125(2):213–20. https://doi.org/10.1111/j.0022-202X.2005.23806.x.

Article  CAS  PubMed  Google Scholar 

Gowayed MA, Mahmoud SA, El-Sayed Y, Abu-Samra N, Kamel MA. Enhanced mitochondrial biogenesis is associated with the ameliorative action of creatine supplementation in rat soleus and cardiac muscles. Exp Ther Med. 2020;19(1):384–92. https://doi.org/10.3892/etm.2019.8173.

Article  CAS  PubMed  Google Scholar 

Hu NJ, Feng GL, Lai XH, Peng M, Song YF. Creatine ameliorates the adverse effects of high-fat diet on hepatic lipid metabolism via activating Mfn2-Mediated mitochondrial fusion in juvenile grass carp. Aquac Nutr. 2025;2025: 1151656. https://doi.org/10.1155/anu/1151656.

Article 

Comments (0)

No login
gif