Boris F Krasnikov
Department of Biochemistry and Molecular Biology, New York Medical College
Dr. Boris F. Krasnikov has received his PhD in Biochemistry at Moscow State University (Moscow, Russia) in 1992. During the following period (up to 2000) he worked as a Research Scientist in the Laboratory of structure and function of mitochondria (Head: Prof. D.B. Zorov) in the Department of Bioenergetics (Head: Prof. V.P. Skulachev) at A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University (Moscow, Russia). Since 2000 Dr. Krasnikov joined Burke Medical Research Institute (Head: Prof. J.P. Blass), White Plains, NY as a Research Scientist worked there till 2007. In 2004 he received a joint appointment as an Instructor in the Department of Neurology and Neuroscience (Head: Prof. M.F. Beal) at Weill Medical College of Cornell University, New York, NY, until 2007. Since 2007 and up to present he is holding position as a Research Assistant Professor in the Department of Biochemistry and Molecular Biology at New York Medical College, Valhalla, NY. Dr. Krasnikov has co-authored more than 30 peer-reviewed original research articles and reviews. He is serving as a reviewer for more than 10 reputed research journals like FEBS Letters, Analytical Biochemistry, American Journal of Physiology, to name a few.
Mitochondria are of immense importance for normal cellular functioning. A key mitochondrial role is energy production through oxidative phosphorylation and oxidation of key biomolecules. Depending on the organ source, a number of other metabolic functions are also carried out by mitochondria (1). Taking into account the unique ability of mitochondria to almost immediately respond even to minute alterations in cell physiology, these organelles can serve as reporters for early-stage changes in cell metabolism. Impairment of mitochondrial functioning is a well-documented phenomenon that occurs under multiple pathophysiological conditions, including cancer (2). Inhibition of the mitochondrial respiratory complexes and ATP synthesis, alteration of mitochondrial membrane potential (ΔΨ), production of reactive oxygen (ROS) and nitrogen (RNS) species, dysregulation of the transport of Ca2+ and other ions, mitochondrial pH imbalance, and induction of the mitochondrial permeability transition (MPT), will lead either to programmed cell death (apoptosis) or necrosis (1-4). Key mitochondria-related cellular parameters, such as levels of ATP and NADH, levels of H2O2, together with key specific mitochondrial parameters, such as O2 uptake, ΔΨ, mitochondrial matrix pH, Ca2+ flux, and swelling of mitochondria, should provide important information linking cell function to mitochondrial function and vice versa under normal and pathological conditions. However, the detailed mechanisms by which the changes in mitochondrial functioning are related to each other are pressing unresolved issues. For many mitochondrial functions in normal cells, there is only a partial understanding of the mechanisms involved in their regulation, and almost nothing is known about these mechanisms in cancer cells (2,3).
For example, we know that mitochondria, as energy producers, are much less efficient in cancer than in normal cells; we also know that mitochondria in cancer cells, compared to normal cells, are much more resistant to Ca2+, ROS, and RNS challenges. It has been shown that elevated amounts of Ca2+ and/or ROS in normal cells induce MPT(5) with concomitant release of cytochrome C from mitochondria, followed by apoptosis (3), but this mitochondrial mechanism is inoperative in cancer cells (2). It has been pointed out that inhibition of the processes and enzymes that participate in cancer cell metabolism (particularly glycolysis) may have a dramatic effect on tumors by limiting cancer cell-specific bioenergetic flow and anabolic reactions, by reversing the neoplastic phenotype and hence stopping growth, by inducing apoptosis, and/or by blocking angiogenesis and invasion (2). However, blocking of glycolysis may have an untoward effect on normal tissues that rely heavily on glycolysis (e.g. skeletal muscle).
Although a link between abnormal mitochondrial metabolism and cancer is quite well recognized, the degree of mitochondrial functional transformation versus tumor aggressiveness has not been established. Thus, understanding i) why cancer cell mitochondria are so resistant to Ca2+, ROS and other inducers of the MPT and ii) how mitochondrial impairment is related to tumor aggressiveness, and targeting these phenomena may lead to the finding of unique/specific strategies that may be useful for the discovery and development of anti-cancer treatments and approaches.