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Morphological analysis of mitochondrial subtypes in the heart

DISCOVERIES (ISSN 2359-7232), 2017, January-March issue

CITATION: 

Kalkhoran SB, Munro P, Qiao F, Ong S, Hall AR, Cabrera-Fuentes H, Chakraborty B, Boisvert WA, Yellon DM, Hausenloy DJ. Unique morphological characteristics of mitochondrial subtypes in the heart: the effect of ischemia and ischemic preconditioning. Discoveries 2017, 5(1): e71 DOI: 10.15190/d.2017.1

Submitted: March 16th, 2017; Revised: March 30th, 2017; Accepted: March 30th, 2017; 

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Unique morphological characteristics of mitochondrial subtypes in the heart: the effect of ischemia and ischemic preconditioning

Siavash Beikoghli Kalkhoran (1,2), Peter Munro (3), Fan Qiao (4), Sang-Bing Ong (5,6), Andrew R. Hall (1,2), Hector Cabrera-Fuentes (5,6,7,8), Bibhas Chakraborty (4), William A. Boisvert (9), Derek M. Yellon (1,2), Derek J. Hausenloy (1,2,5,6,10,11,*)

(1) The Hatter Cardiovascular Institute, University College London, UK;

(2) The National Institute of Health Research University College London Hospitals Biomedical Research Centre, UK;

(3) Institute of Ophthalmology, University College London, UK;

(4) Centre for Quantitive Medicine, Duke-NUS Graduate Medical School, Singapore;

(5) Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore;

(6) National Heart Research Institute Singapore, National Heart Centre Singapore; 

(7) Kazan Federal University, Department of Microbiology, Kazan, Russian Federation;

(8) Escuela de Ingenieria y Ciencias, Centro de Biotecnologia-FEMSA, Tecnologico de Monterrey, Mexico;

(9) Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii;

(10) Yong Loo Lin School of Medicine, National University Singapore, Singapore;

(11) Barts Heart Centre, St Bartholomew’s Hospital, London, UK;

*Correspondence to: Derek J Hausenloy, MD, Cardiovascular & Metabolic Diseases Program, Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore 169857; E-mail: derek.hausenloy@duke-nus.edu.sg;

Abstract

Rationale: Three subsets of mitochondria have been described in adult cardiomyocytes - intermyofibrillar (IMF), subsarcolemmal (SSM), and perinuclear (PN). They have been shown to differ in physiology, but whether they also vary in morphological characteristics is unknown. Ischemic preconditioning (IPC) is known to prevent mitochondrial dysfunction induced by acute myocardial ischemia/reperfusion injury (IRI), but whether IPC can also modulate mitochondrial morphology is not known. 

Aims: Morphological characteristics of three different subsets of adult cardiac mitochondria along with the effect of ischemia and IPC on mitochondrial morphology will be investigated.

Methods: Mouse hearts were subjected to the following treatments (N=6 for each group): stabilization only, IPC (3x5 min cycles of global ischemia and reperfusion), ischemia only (20 min global ischemia); and IPC and ischemia. Hearts were then processed for electron microscopy and mitochondrial morphology was assessed subsequently.

Results: In adult cardiomyocytes, IMF mitochondria were found to be more elongated and less spherical than PN and SSM mitochondria. PN mitochondria were smaller in size when compared to the other two subsets. SSM mitochondria had similar area to IMF mitochondria but their sphericity measures were similar to PN mitochondria. Ischemia was shown to increase the sphericity parameters of all 3 subsets of mitochondria; reduce the length of IMF mitochondria, and increase the size of PN mitochondria. IPC had no effect on mitochondrial morphology either at baseline or after ischemia.     

Conclusion: The three subsets of mitochondria in the adult heart are morphologically different. IPC does not appear to modulate mitochondrial morphology in adult cardiomyocytes.

Access full text of the manuscript here:    Suppl. Information (pdf)

References

1. Ong S-B, Hall AR, Hausenloy DJ. Mitochondrial dynamics in cardiovascular health and disease. Antioxid Redox Signal. 2013;19(4):400–14. 

2. Hollander JM, Thapa D, Shepherd DL. Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies. Am J Physiol Heart Circ Physiol. 2014 Jul 1;307(1):H1-14. 

3. Palmer JW, Tandler B, Hoppel CL. Biochemical differences between subsarcolemmal and interfibrillar mitochondria from rat cardiac muscle: effects of procedural manipulations. Arch Biochem Biophys. 1985 Feb;236(2):691–702. 

4. Suh JH, Heath S-H, Hagen TM. Two subpopulations of mitochondria in the aging rat heart display heterogenous levels of oxidative stress. Free Radic Biol Med. 2003 Nov 1;35(9):1064–72. 

5. Holmuhamedov EL, Oberlin A, Short K, Terzic A, Jahangir A. Cardiac subsarcolemmal and interfibrillar mitochondria display distinct responsiveness to protection by diazoxide. PLoS One. 2012;7(9):e44667. 

6. Palmer JW, Tandler B, Hoppel CL. Biochemical differences between subsarcolemmal and interfibrillar mitochondria from rat cardiac muscle: effects of procedural manipulations. Arch Biochem Biophys. 1985 Feb 1;236(2):691–702. 

7. Gustafsson R, Tata JR, Lindberg O, Ernster L. The relationship between the structure and activity of rat skeletal muscle mitochondria after thyroidectomy and thyroid hormone treatment. J Cell Biol. 1965 Aug;26(2):555–78. 

8. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986 Nov;74(5):1124–36. 

9. Cabrera-Fuentes HA, Aragones J, Bernhagen J, Boening A, Boisvert WA, Bøtker HE, et al. From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”. Basic Res Cardiol. 2016 Nov;111(6):69. 

10. Cabrera-Fuentes HA, Alba-Alba C, Aragones J, Bernhagen J, Boisvert WA, Bøtker HE, et al. Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside. Basic Res Cardiol. 2016 Jan;111(1):7. 

11. Kamga Pride C, Mo L, Quesnelle K, Dagda RK, Murillo D, Geary L, et al. Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion. Cardiovasc Res. 2014 Jan 1;101(1):57–68. 

12. Ong S-B, Hall AR, Dongworth RK, Kalkhoran S, Pyakurel A, Scorrano L, et al. Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology. Thromb Haemost. 2015 Mar;113(3):513–21. 

13. Palmer JW, Tandler B, Hoppel CL. Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. J Biol Chem. ASBMB; 1977 Dec;252(23):8731–9. 

14. Shin G, Sugiyama M, Shoji T, Kagiyama A, Sato H, Ogura R. Detection of mitochondrial membrane damages in myocardial ischemia with ESR spin labeling technique. J Mol Cell Cardiol. 1989 Oct;21(10):1029–36. 

15. Birkedal R, Shiels H a, Vendelin M. Three-dimensional mitochondrial arrangement in ventricular myocytes: from chaos to order. Am J Physiol Cell Physiol. 2006 Dec;291(6):C1148-58. 

16. Fawcett DW, McNutt NS. The ultrastructure of the cat myocardium. I. Ventricular papillary muscle. J Cell Biol. 1969 Jul;42(1):1–45. 

17. Picard M, White K, Turnbull DM. Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study. J Appl Physiol. 2013 Jan;114(2):161–71. 

18. Shimada T, Horita K, Murakami M, Ogura R. Morphological studies of different mitochondrial populations in monkey myocardial cells. Cell Tissue Res. 1984;238(3):577–82. 

19. Collins TJ, Berridge MJ, Lipp P, Bootman MD. Mitochondria are morphologically and functionally heterogeneous within cells. EMBO J. 2002 Apr 2;21(7):1616–27. 

20. Riva A, Tandler B, Loffredo F, Vazquez E, Hoppel C. Structural differences in two biochemically defined populations of cardiac mitochondria. Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H868-72. 

21. Duan JM, Karmazyn M. Acute effects of hypoxia and phosphate on two populations of heart mitochondria. Mol Cell Biochem. 1989 Oct 5;90(1):47–56. 

22. Wollenbeerger A, Schulze W. Mitochondrial alterations in the myocardium of dogs with aortic stenosis. J Biophys Biochem Cytol. 1961 Jun 2;10(3):285–8. 

23. Dabkowski ER, Baseler W a, Williamson CL, Powell M, Razunguzwa TT, Frisbee JC, et al. Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H529-40. 

24. Ahmad T, Aggarwal K, Pattnaik B, Mukherjee S, Sethi T, Tiwari BK, et al. Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death Dis. Nature Publishing Group; 2013;4(1):e461. 

25. Reis Y, Bernardo-Faura M, Richter D, Wolf T, Brors B, Hamacher-Brady A, et al. Multi-parametric analysis and modeling of relationships between mitochondrial morphology and apoptosis. PLoS One. 2012;7(1). 

26. Akao M, O’Rourke B, Teshima Y, Seharaseyon J, Marbán E. Mechanistically distinct steps in the mitochondrial death pathway triggered by oxidative stress in cardiac myocytes. Circ Res. 2003;92(2):186–94. 

27. Liu X, Hajnóczky G. Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ. 2011;18(10):1561–72. 

28. Lesnefsky EJ, Slabe TJ, Stoll MS, Minkler PE, Hoppel CL. Myocardial ischemia selectively depletes cardiolipin in rabbit heart subsarcolemmal mitochondria. Am J Physiol Heart Circ Physiol. 2001;280(6):H2770-8. 

29. Dague E, Genet G, Lachaize V, Guilbeau-Frugier C, Fauconnier J, Mias C, et al. Atomic force and electron microscopic-based study of sarcolemmal surface of living cardiomyocytes unveils unexpected mitochondrial shift in heart failure. J Mol Cell Cardiol. Elsevier Ltd; 2014 Sep;74:162–72. 

30. Sun J, Nguyen T, Aponte AM, Menazza S, Kohr MJ, Roth DM, et al. Ischaemic preconditioning preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria. Cardiovasc Res. 2015 May;106(2):227–36. 

31. Kurian GA, Berenshtein E, Saada A, Chevion M. Rat cardiac mitochondrial sub-populations show distinct features of oxidative phosphorylation during ischemia, reperfusion and ischemic preconditioning. Cell Physiol Biochem. 2012;30(1):83–94. 

32. Hoppel CL, Tandler B, Fujioka H, Riva A. Dynamic organization of mitochondria in human heart and in myocardial disease. Int J Biochem Cell Biol. 2009 Oct;41(10):1949–56. 

33. Sharp WW, Fang YH, Han M, Zhang HJ, Hong Z, Banathy A, et al. Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission. FASEB J. 2014 Jan;28(1):316–26. 

34. Ong S-B, Subrayan S, Lim SY, Yellon DM, Davidson SM, Hausenloy DJ. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010 May;121(18):2012–22. 

35. Disatnik M-H, Ferreira JCB, Campos JC, Gomes KS, Dourado PMM, Qi X, et al. Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction. J Am Heart Assoc. 2013 Oct;2(5):e000461. 

36. Shen AC, Jennings RB. Myocardial calcium and magnesium in acute ischemic injury. Am J Pathol. 1972 Jun;67(3):417–40. 

37. Kloner RA, Fishbein MC, Braunwald E, Maroko PR. Effect of propranolol on mitochondrial morphology during acute myocardial ischemia. Am J Cardiol. 1978 May 1;41(5):880–6. 

38. Cellier L, Tamareille S, Kalakech H, Guillou S, Lenaers G, Prunier F, et al. Remote Ischemic Conditioning Influences Mitochondrial Dynamics. Shock. 2015;45(2):1. 

39. Vélez DE, Hermann R, Barreda Frank M, Mestre Cordero VE, Savino EA, Varela A, et al. Effects of wortmannin on cardioprotection exerted by ischemic preconditioning in rat hearts subjected to ischemia-reperfusion. J Physiol Biochem. 2016 Mar;72(1):83–91. 

40. Zhao Z, Cui W, Zhang H, Gao H, Li X, Wang Y, et al. Pre-treatment of a single high-dose of atorvastatin provided cardioprotection in different ischaemia/reperfusion models via activating mitochondrial KATP channel. Eur J Pharmacol. 2015 Mar 15;751:89–98. 

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