2^nd World Congress on
Anatomy and Physiology

Dr. Sabzali Javadov

Professor, Department of Physiology,

University of Puerto Rico School of Medicine,

USA

Biography

Dr. Javadov received his MD from the Russian Medical University, Moscow (1983), PhD from the Russian Cardiology Center, Moscow (1986), and DSc from the Moscow University (1992). He worked as a Postdoctoral Researcher and a Visiting Scientist at the Magdeburg Medical University, Germany (1987), National Institute of Cardiology, Hungary (1991), University of Bristol, England (1997-2001), and Western University, Canada (2003-2008). Since 2009, he is a Professor of the Department of Physiology at the University of Puerto Rico School of Medicine, USA. Dr. Javadov has specific training and expertise in cardiac biochemistry and physiology with a focus on the role of mitochondria in cardiac dysfunction induced by ischemia-reperfusion and heart failure. Currently, his laboratory elucidates the relationship between mitochondrial ROS, permeability transition, and electron transport chain supercomplexes in myocardial infarction. Dr. Javadov has published over 100 papers in reputed journals and books and has been serving as an editorial board member for several biomedical journals.

Research Area

We elucidate molecular mechanisms of mitochondria-mediated cardiac dysfunction during coronary heart diseases such as myocardial infarction (MI) and heart failure (HF). Timely restoration of coronary perfusion known as reperfusion is the only effective therapeutic intervention for protecting the heart from MI (ischemic injury). Currently, there is no effective therapy for preventing cardiac ischemia (infarction)-reperfusion (IR) injury. The loss of mitochondrial function plays a crucial role in IR-induced cell death suggesting that protection and restoration of mitochondrial function is pivotal to cell survival in the heart. However, limited knowledge of the mechanisms underlying mitochondria-mediated cell death obscures the development of new mitochondria-targeted cardioprotective compounds. The main goal of these studies is to develop new therapeutic strategies to prevent myocardial injury, and improve clinical outcomes in patients with post-MI and HF through targeting mitochondria. Cardiac IR increases Ca2+, ROS, and Pi levels in mitochondria that, in turn, induce permeability transition pore (PTP) opening in the inner mitochondrial membrane (IMM). In addition, high mitROS oxidize cardiolipin (CL), a mitochondrial signature phospholipid, which, in turn, may facilitate degradation of supercomplexes (SCs), large multiprotein complexes containing individual electron transport chain (ETC) complexes. According to the solid-state model, the assembly of SCs provides high-efficiency electron flux throughout the ETC; it increases ATP synthesis and significantly reduces electron leakage and mtROS production due to short diffusion distances between ETC complexes. The cause-and-effect relationship between PTP induction and SC degradation has not yet been established. Based on our recent studies (Jang et al, 2017, Jang & Javadov, 2017), we propose that the PTP opening causes disintegration of mitochondrial SCs, leading to diminished energy metabolism and cell death during cardiac IR. PTP-induced mitochondrial swelling induces remodeling of the inner mitochondrial membrane and thus, sensitizes CL to the ROS attack leading to degradation of SCs. Understanding the role of PTP-dependent and PTP-independent ROS in the disintegration of SCs can provide new insights into the molecular basis of mitochondria-mediated cell death during cardiac IR. Importantly, elucidation of pathophysiological consequences of oxidative stress and validation of molecular targets in mitochondria are very important for the development of new cardioprotective agents. We propose that simultaneous inhibition of PTP-induced mitochondrial swelling and ROS production can exert synergistic effects against cardiac IR injury and thus, enable us to develop new therapeutic strategies targeting mitochondria.