Changes in mitochondrial morphology and organization can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy

被引:33
作者
Jarosz, Jan [1 ,2 ]
Ghosh, Shouryadipta [1 ,2 ]
Delbridge, Lea M. D. [3 ]
Petzer, Amorita [4 ]
Hickey, Anthony J. R. [4 ]
Crampin, Edmund J. [2 ,5 ,6 ,7 ]
Hanssen, Eric [8 ]
Rajagopal, Vijay [1 ,2 ]
机构
[1] Univ Melbourne, Dept Mech Engn, Cell Struct & Mechanobiol Grp, Parkville, Vic, Australia
[2] Univ Melbourne, Melbourne Sch Engn, Syst Biol Lab, Parkville, Vic, Australia
[3] Univ Melbourne, Dept Physiol, Parkville, Vic, Australia
[4] Univ Auckland, Sch Biol Sci, Auckland, New Zealand
[5] Univ Melbourne, Fac Sci, Sch Math & Stat, Parkville, Vic, Australia
[6] Univ Melbourne, Fac Med Dent & Hlth Sci, Sch Med, Parkville, Vic, Australia
[7] Univ Melbourne, ARC Ctr Excellence Convergent Bionano Sci & Tec, Parkville, Vic, Australia
[8] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Adv Microscopy Facil, Parkville, Vic, Australia
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2017年 / 312卷 / 02期
关键词
diabetic cardiomyopathy; oxidative phosphorylation; mitochondrion dynamics; cardiac ultrastructure; CARDIAC MITOCHONDRIA; HEART; MODEL; RATS; MEMBRANE; DYNAMICS; STRESS; CARDIOMYOCYTES; SUBPOPULATIONS; RESPIRATION;
D O I
10.1152/ajpcell.00298.2016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:C190 / C197
页数:8
相关论文
共 41 条
  • [1] Compartmentalized energy transfer in cardiomyocytes: Use of mathematical modeling for analysis of in vivo regulation of respiration
    Aliev, MK
    Saks, VA
    [J]. BIOPHYSICAL JOURNAL, 1997, 73 (01) : 428 - 445
  • [2] Protective Mechanisms of Mitochondria and Heart Function in Diabetes
    Aon, Miguel A.
    Tocchetti, Carlo G.
    Bhatt, Niraj
    Paolocci, Nazareno
    Cortassa, Sonia
    [J]. ANTIOXIDANTS & REDOX SIGNALING, 2015, 22 (17) : 1563 - 1586
  • [3] Battiprolu PK, 2010, DRUG DISCOV TODAY DI, V7, pe135, DOI [10.1016/j.ddmec.2010.08.001, DOI 10.1016/J.DDMEC.2010.08.001]
  • [4] A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation
    Beard, DA
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2005, 1 (04) : 252 - 264
  • [5] Beer F.P., 2006, Mechanics of Materials
  • [6] Mitochondria in the diabetic heart
    Bugger, Heiko
    Abel, E. Dale
    [J]. CARDIOVASCULAR RESEARCH, 2010, 88 (02) : 229 - 240
  • [7] Diabetic cardiomyopathy-associated dysfunction in spatially distinct mitochondrial subpopulations
    Dabkowski, Erinne R.
    Williamson, Courtney L.
    Bukowski, Valerie C.
    Chapman, Rebecca S.
    Leonard, Stephen S.
    Peer, Cody J.
    Callery, Patrick S.
    Hollander, John M.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2009, 296 (02): : H359 - H369
  • [8] Myocardial autophagic energy stress responses-macroautophagy, mitophagy, and glycophagy
    Delbridge, Lea M. D.
    Mellor, Kimberley M.
    Taylor, David J. R.
    Gottlieb, Roberta A.
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2015, 308 (10): : H1194 - H1204
  • [9] Mitochondrial dynamics in heart disease
    Dorn, Gerald W., II
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2013, 1833 (01): : 233 - 241
  • [10] Fitzl G, 2001, EXP TOXICOL PATHOL, V52, P557, DOI 10.1016/S0940-2993(01)80017-8