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

CITATION: 

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.

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