Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(4): 87-104


О.V. Кolomiets , Yu.V. Danylovych, Н.V. Danylovych, S.О. Кosterin

    Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine


The review analyzed published data about transport of ions of calcium in the mitochondria and presented some own results of experiments conducted on the smooth muscle of the uterus (myometrium). In particular, it was described the systems of mitochondrial Са2+- uniporter, «rapid mode uptake», mitochondrial ryanodine receptor, Na+-Са2+- and Н+-Са2+- exchangers, mitochondrial permeability transition pore. The possible functional role of Са2+ in mitochondria and their significance in maintaining of cell’s Са2+-homeostasis have been considered. The features of transmembrane exchange of Ca2 + in mitochondria for various pathologies was discussed.

Keywords: mitochondria; Са2+-uniporter; «rapid mode uptake»; mitochondrial ryanodine receptor; Na+-Са2+-exchanger; Н+-Са2+-exchanger; mitochondrial permeability transition pore; smooth muscle; myometrium.


  1. Kostyuk PG, Kostyuk OP, Lukyanets EA. Intracellular calcium signaling: structures and functions. Kiev: Nauk. Dumka; 2010. [Ukrainian]. PubMedCentral
  3. Santo-Domingo J, Demaurex N. Calcium uptake mechanisms of mitochondria. Biochim Biophys Acta. 2010; 1797(6-7):907-12. CrossRef PubMed
  5. Kosterin SA, Burdyga ThV. Transport and intracellular homeostasis of Sa2+ in myometrium. Biol Bul Rev. 1993;113(4) :485-506. [Russian].
  6. Bernardi P, Rasola A. Calcium and cell death: the mitochondrial connection. Subcell Biochem. 2007;45:481-506. CrossRef PubMed
  8. Chalmers S, Nicholls DG. The relationship between free and total calcium concentrations in the matrix of liver and brain mitochondria. J Biol Chem 2003;278(21):19062-70. CrossRef PubMed
  10. Rizzuto R., Marchi S., Bonora M., Aguiary P., Bononi A. Ca2+ transfer from the ER to mitochondria: When, how and why. Biochim Biophys Acta. 2009;1787(11):1342-51. CrossRef PubMed PubMedCentral
  12. Graier WF, Frieden M, Malli R.. Mitochondria and Ca2+ signaling: old quests, new functions. Eur J Physiol. 2007;455(3):375-96. CrossRef PubMed PubMedCentral
  14. Takeuchi A, Kim B, Matsuoka S. The destiny of Ca2+ released by mitochondria. J Physiol Sci. 2015;65(1):11-24. CrossRef PubMed PubMedCentral
  15. Gunter TE, Pfeiffer DR. Mechanisms by which mitochondrria transport calcium. Am J Physiol. 1990;258(5 Pt 1):C755-86.
  17. DeLuca HF, Engstrom GW. Calcium uptake by rat kidney mitochondria. Proc Nat Acad Sci USA. 1961;47(11): 1744-1750. CrossRef  
  18. Lehninger A. L, Rossi CS, Greenawalt JW. Respirationdependent accumulation of inorganic phosphate and Ca ion by rat liver mitochondria. Biochem Biophys Rec Commun. 1963;10(3):444-8. CrossRef  
  19. Carafoli E, Rossi CS, Lehninger AL. Uptake of adenine nucleotides by respiring mitochondria during active accumulation of Ca2+ and phosphate. J Biol Chem. 1965;240(5):2254-61. PubMed
  21. Kosterin SO. Transport of calcium in the smooth muscles. Kiev: Nauk. Dumka; 1990. [Russian].
  23. Pan S, Ryu S-Y, Sheu S-S. Distinctive characteristics and functions of multiple mitochondrial Ca2+ influx mechanisms. Sci China Life Sci. 2011;54(8):763-9. CrossRef PubMed PubMedCentral
  25. Szabadkai G, Duchen MR. Mitochondria: The Hub of Cellular Ca2+ Signaling. Physiol. 2008; 23(2):84-94. CrossRef PubMed
  27. Vernardi R. Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev. 1999;79(4):1127-55. CrossRef PubMed
  29. Malli R, Graier WF. Mitochondrial Ca2+ channels: Great unknowns with important functions. FEBS Lett. 2010;584(10):1942-7. CrossRef PubMed PubMedCentral
  31. Feissner RF, Skalska J, Gaum WE, Sheu SS.Crosstalk signaling between mitochondrial Ca2+ and ROS. Front Biosci. 2009;14:1197-218. CrossRef  
  32. Veklich TO. Transport of Ca2+ in the smooth muscle cells mitochondria: Manuscript. Kiev: Palladin Institute of Biochemistry of the NASU; 2003. [Ukrainian].
  34. Ryu SY, Beutner G, Dirksen RT, Kinnally KW, Sheu SS. Mitochondrial ryanodine receptors and other mitochondrial Ca2+ permeable shannels. FEBS Lett. 2010;584(10):1948-55. CrossRef PubMed PubMedCentral
  36. Gunter TE, Yule DI, Gunter KK, Eliseev RA, Salter JD. Calcium and mitochondria. FEBS Letters. 2004;567(1):96- CrossRef PubMed
  38. Hoppe UC. Mitochondrial calcium channels. FEBS Lett. 2010;584(10):1975-81. CrossRef PubMed
  40. Csordás G, Várnai P, Golenár T, Sheu S-S, Hajnóczky G. Calcium transport across the inner mitochondrial membrane: molecular mechanisms and pharmacology. Mol Cell Endocrinol. 2012; 353(1-2):109-13. CrossRef PubMed PubMedCentral
  42. Akopova OV, Sahach VF. The influence of nitric oxide donors on Ca2+-uptake in rat heart and liver mitochondria. Ukr Biokhim Zh. 2005;77(2):82-7. [Russian].
  44. Danylovych YuV, Kolomiets' OV, Danylovych GV, Kosterin SO. Nitric oxide as a possible regulator of energydependent Ca2+ transport in mitochondria of uterine smooth muscle. Fiziol Zh. 2014;60(2):12-7. [Ukrainian]. PubMed
  46. Kolomiets OV, Danylovych YuV, Danylovych GV, Kosterin SO. Ca2+ accumulation study in isolated smooth muscle mitochondria using Fluo-4 AM. Ukr Biokhim Zh 2013;85(4):30-9. [Ukrainian].
  47. Kolomiets' OV, Danylovych YuV, Danylovych GV, Kosterin SO. Ca2+/H+-exchange in myometrium mitochondria. Ukr Biochem J. 2014;86(3):41-8. [Ukrainian]. CrossRef  
  48. Foskett JK, Philipson B. The Mitochondrial Ca2+ Uniporter Complex. J Mol Cell Cardiol. 2015;78:3-8. CrossRef PubMed PubMedCentral
  50. De Stefani D, Patron M, Rizzuto R. Structure and function of the Mitochondrial Calcium Uniporter complex. Biochim Biophys Acta. 2015;1853(9):2006-11. CrossRef PubMed PubMedCentral
  52. Santo-Domingo J, Wiederkehr A, De Marchi U. Modulation of the matrix redox signaling by mitochondrial Ca2+. World J Biol Chem. 2015;6(4):310-23. CrossRef PubMed PubMedCentral
  54. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK. Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature. 2011;476(7360):341-5. CrossRef PubMed PubMedCentral
  56. Bernardi P, von Stockum S. The permeability transition pore as a Ca2+ release channel: New answers to an old question. Cell Calcium. 2012;52(1):22-7. CrossRef PubMed PubMedCentral
  58. Rasola A, Bernardi P. Mitochondrial permeability transition in Ca2+-dependent apoptosis and necrosis. Cell Calcium. 2011;50(3):222-33. CrossRef PubMed
  60. Kursky MD, Kosterin SA, Burchinskaya NF, Shlykov SG. Passive transport of Sa2+ into fractions of myometrium mitochondria. Ukr Biokhim Zh. 1987;59(3):35-9. [Russian].
  61. Kolomiets' OV, Danylovych YuV, Danylovych GV. H+- Ca2+-exchanger in the myometrium mitochondria: modulation of exogenous and endogenous compounds. Fiziol Zh. 2014;60(5):33-42. [Ukrainian].
  63. Palty R, Hershfinkel M, Sekler I. Molecular Identity and Functional Properties of the Mitochondrial Na+/Ca2+ Exchanger. J Biol Chem. 2012;287(38):31650-7. CrossRef PubMed PubMedCentral
  65. Nowikovsky K, Pozzan T, Rizzuto R, Scorrano L, Bernardi P. The pathophysiology of LETM1. J Gen Physiol. 2012;139(6):445-54. CrossRef PubMed PubMedCentral
  67. Jiang D, Zhao L, Clapham DE. Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter. Science. 2009;326(5949):144-7. CrossRef PubMed PubMedCentral
  69. Vinogradov AD. Energy transduction in mitochondria. Soros Educ J. 1999 (9):11-19.
  71. Wingrove DE, Gunter TE. Kinetics of mitochondrial calcium transport. I. Characteristics of the sodium-independent calcium efflux mechanism of liver mitochondria. J Biol Chem. 1986;261(32):15159-65. PubMed
  73. Vovkanych LS, Dubytsky LO. Kinetical properties of the H+-stimulated rat liver mitochondria Ca2+ efflux. Exp Clin Physiol Biochem 2001;15(3):34-37. [Ukrainian].
  74. Tsai MF, Jiang D, Zhao L, Clapham D, Miller C. Functional reconstitution of the mitochondrial Ca2+/H+ antiporter Letm1. J Gen Physiol. 2014;143(1):67-73. CrossRef PubMed PubMedCentral
  76. Schlickum S, Moghekar A, Simpson JC, Steglich C, O'Brien RJ, Winterpacht A, Endele SU. LETM1, a gene deleted in Wolf-Hirschhorn syndrome, encodes an evolutionarily conserved mitochondrial protein. Genomics. 2004;83(2):254-61. CrossRef PubMed
  78. Dimmer KS, Navoni F, Casarin A, Trevisson E, Endele S, Winterpacht A, Salviati L, Scorrano L. LETM1, deleted in Wolf-Hirschhorn syndrome is required for normal mitochondrial morphology and cellular viability. Hum Mol Genet. 2008;17(2):201-14. CrossRef PubMed
  80. Shao J, Fu Z, Ji Y, Guan X, Guo S, Ding Z, Yang X, Cong Y, Shen Y. Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca2+/H+ antiporter. Sci Rep. 2016;6:34174. CrossRef PubMed PubMedCentral
  82. Piao L, Li Y, Kim SJ, Byun HS, Huang SM. Association of LETM1 and MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death. Cancer Res. 2009;69(8):3397-404. CrossRef PubMed
  84. Doonan PJ, Chandramoorthy HC, Hoffman NE, Zhang X, Cárdenas C, Shanmughapriya S, Rajan S, Vallem S, Chen X, Foskett JK, Cheung JY, Houser SR, Madesh M. LETM1-dependent mitochondrial Ca2+ flux modulates cellular bioenergetics and proliferation. FASEB J. 2014;28(11):4936-49. CrossRef PubMed PubMedCentral
  85. Akopova OV. The role of permeability transition pore in transmembrane Ca2+-exchange in mitochondria. Ukr Biokhim Zh. 2008;80(3):40-47. [Ukrainian]. Giulivi C, Kato K, Cooper CE. Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol. 2006;291(6):C1225-31.
  87. Llorente-Folch I, Rueda CB, Pardo B, Szabadkai G, Duchen MR, Satrustegui J. The regulation of neuronal mitochondrial metabolism by calcium. J Physiol. 2015;593(16):3447-62. CrossRef PubMed PubMedCentral
  88. Giulivi C, Kato K, Cooper CE. Nitric oxide regulation of mitochondrial oxygen consumption I: cellular physiology. Am J Physiol Cell Physiol. 2006;291(6):C1225-31. CrossRef  
  89. Danylovych YuV, Karakhim SA, Danylovych HV, Kolomiets OV, Kosterin SO. Electrochemical potential of the inner mitochondrial membrane and Ca2+ homeostasis of myometrium cells. Ukr Biochem J. 2015;87(5):61-71. CrossRef  
  90. Campos JC, Bozi LH, Bechara LR, Lima VM, Ferreira JC. Mitochondrial Quality Control in Cardiac Diseases. Front Physiol. 2016;7:479. CrossRef PubMed PubMedCentral
  92. El-Hattab AW, Scaglia F. Mitochondrial Cardiomyopathies. Front Cardiovasc Med. 2016;3:25. CrossRef  
  93. Picard M, Wallace DC, Burelle Y. The rise of mitochondria in medicine. Mitochondrion. 2016;30:105-16. CrossRef PubMed PubMedCentral
  95. Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta. 2015;1847(11):1424-33. CrossRef PubMed PubMedCentral
  97. Niyazov DM, Kahler SG, Frye RE. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Mol Syndromol. 2016;7(3):122-37. CrossRef PubMed PubMedCentral
  99. Pathak D, Berthet A, Nakamura K. Energy failure: does it contribute to neurodegeneration? Ann Neurol. 2013;74(4):506-16. CrossRef PubMed PubMedCentral
  101. Calì T, Ottolini D, Brini M. See comment in PubMed Commons belowCell Calcium. Mitochondrial Ca2+ and neurodegeneration. Cell Calcium. 2012;52(1):73-85. CrossRef PubMed PubMedCentral
  103. Görlach A, Bertram K, Hudecova S, Krizanova O. Calcium and ROS: A mutual interplay. Redox Biol. 2015;6:260-71. CrossRef PubMed PubMedCentral
  105. Maléth J, Hegyi P. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview. Philos Trans R Soc Lond B Biol Sci. 2016;371(1700) .
  107. Cui C, Merritt R, Fu L, Pan Z. Targeting calcium signaling in cancer therapy. Acta Pharm Sin B. 2017;7(1):3-17. CrossRef PubMed PubMedCentral
  109. Rimessi A, Patergnani S, Bonora M, Wieckowski MR, Pinton P. Mitochondrial Ca2+ Remodeling is a Prime Factor in Oncogenic Behavior. Front Oncol. 2015;5:143. CrossRef PubMed PubMedCentral
  111. Rasola a, Bernardi P. The mitochondrial permeability transition pore and its adaptive responses in tumor cells. Cell Calcium. 2014; 56(6): 437–445. CrossRef PubMed PubMedCentral
  113. Logan CV, Szabadkai G, Sharpe JA et al. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling. Nat Genet. 2014;46(2):188-93. CrossRef PubMed
  115. Lewis-Smith D, Kamer KJ, Griffin H. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurol Genet. 2016;2(2):e59. CrossRef PubMed PubMedCentral

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.