title: Changes in mitochondrial morphology and organization can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy.
abstract: Diabetic cardiomyopathy is accompanied by metabolic and ultrastructural alterations, but the impact of the structural changes on metabolism itself is yet to be determined. Morphometric analysis of mitochondrial shape and spatial organization within transverse sections of cardiomyocytes from control and streptozotocin-induced type I diabetic Sprague-Dawley rats revealed that mitochondria are 20% smaller in size while their spatial density increases by 53% in diabetic cells relative to control myocytes. Diabetic cells formed larger clusters of mitochondria (60% more mitochondria per cluster) and the effective surface-to-volume ratio of these clusters increased by 22.5%. Using a biophysical computational model we found that this increase can have a moderate compensatory effect by increasing the availability of ATP in the cytosol when ATP synthesis within the mitochondrial matrix is compromised.
authors.affiliation: Cell Structure and Mechanobiology Group, Department of Mechanical Engineering, University of Melbourne, Parkville, Australia.|Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Australia.
authors.forename: Jan
authors.initials: J
authors.lastname: Jarosz
authors.affiliation: Cell Structure and Mechanobiology Group, Department of Mechanical Engineering, University of Melbourne, Parkville, Australia.|Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Australia.
authors.forename: Shouryadipta
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Physiology, University of Melbourne, Parkville, Australia.
authors.forename: Lea M D
authors.initials: LM
authors.lastname: Delbridge
authors.affiliation: School of Biological Sciences, University of Auckland, Aukland, New Zealand.
authors.forename: Amorita
authors.initials: A
authors.lastname: Petzer
authors.affiliation: School of Biological Sciences, University of Auckland, Aukland, New Zealand.
authors.forename: Anthony J R
authors.initials: AJ
authors.lastname: Hickey
authors.affiliation: Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Australia.|School of Mathematics and Statistics, Faculty of Science, University of Melbourne, Parkville, Australia.|School of Medicine, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia; and.
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Crampin
authors.affiliation: Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Australia.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0002-4064-1844
authors.initials: E
authors.lastname: Hanssen
authors.affiliation: Cell Structure and Mechanobiology Group, Department of Mechanical Engineering, University of Melbourne, Parkville, Australia; vijay.rajagopal@unimelb.edu.au.|Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, Parkville, Australia.
authors.forename: Vijay
authors.identifier: http://orcid.org/0000-0002-5509-402X
authors.initials: V
authors.lastname: Rajagopal
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D003198:Computer Simulation; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology*; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D008955:Models, Cardiovascular; D010085:Oxidative Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000255:Adenosine Triphosphate
keywords: cardiac ultrastructure; diabetic cardiomyopathy; mitochondrion dynamics; oxidative phosphorylation