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SPINE AND SPINAL DISORDERS
5
th
World Congress on
Spine 2019
October 16-17, 2019
Volume 03
Journal of Neurology and Clinical Neuroscience
J Neurol Clin Neurosci, Volume 03
October 16-17, 2019 | Rome, Italy
Mitochondrial respiratory supercomplexes in the Heart: Physiological and
pathophysiological roles
Background
: Mitochondria as a powerhouse play a central role in both physiology and pathophysiology of the heart. They are
involved in the pathogenesis of human diseases and aging, particularly coronary heart diseases such as Myocardial Infarction and
Ischemia-Reperfusion (IR). Coronary Heart Diseases are the leading cause of morbidity and mortality worldwide, accounting
for over 370,000 deaths per year in the USA. Despite intensive studies, molecular mechanisms of mitochondria-mediated cell
death and heart dysfunction induced by cardiac IR remains unknown. Here, we elucidated the role of mitochondrial Respiratory
Super-Complexes (RSC), the supramolecular complexes containing individual Electron Transport Chain (ETC) complexes I, III
and V, under physiological conditions and in response to cardiac IR injury.
Methods
: Studies were carried out in wild-type adult male mice/rats and Tafazzin knockdown mice. We utilized
in vivo
(intact
heart) and
in vitro
(cultured cardiomyocytes) models using a wide range of genetic, biochemical and physiological approaches.
Results
: We demonstrate that: i) Sustained reperfusion after
ex-vivo
global ischemia induces disintegration of RSCs prevented
by inhibition of the Mitochondrial Permeability Transition Pore (MPTP) opening and ROS production, ii) MPTP-dependent
mitochondrial swelling stimulates cleavage of the Optic Atrophy 1 (OPA1) protein, which plays an important role in
mitochondrial fusion as well as in the maintenance of cristae structure, iii) OPA1 silencing provokes RSC disassembly associated
with reduction in the activity of individual ETC complexes, iv) Downregulation of the ETC complex I subunit NDUFA11 but
not SDHC subunit of complex II diminishes the structural integrity of RSC; v) Downregulation of Cardiolipin synthesis in
Tafazzin knockdown mice reduces RSC levels and ETC complexes activity and vi) RSC disassembly induced by chemical
treatment does not correlate with cardiac function.
Conclusion
: ETC complex I and Cardiolipin are involved in RSC formation and MPTP-induced mitochondrial swelling
stimulates RSC disassembly in cardiac IR injury.
Biography
Sabzali Javadov has specific training and broad expertise in cardiac Biochemistry and Physiology with a focus on the role of mitochondria in
Cardiac Dysfunction induced by Ischemia-Reperfusion, post-infarction heart failure and aging. His studies have been conducted on various
animal and cell model systems using a wide range of genetic, biochemical and physiological approaches. Currently, his laboratory elucidates
the relationship between mitochondrial reactive oxygen species, permeability transition and electron transport chain supercomplexes in the
heart. These studies are useful for the development of new mitochondria-targeting pharmacological compounds to prevent Coronary Heart
Diseases. He has published over 100 papers in reputed journals and books and has been serving as an editorial board member for several
biomedical journals.
e
:
sabzali.javadov@upr.eduSabzali Javadov
University of Puerto Rico School of Medicine, USA