Faculty and Research Interests
Dmitriy Markov, PhD
Science Center 203B
856-566-6915 - office; 856-566-6403 - lab
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia, 2000, PhD in Biology.
Department of Biology, Lomonosov Moscow State University, Russia, 1994, BS in Biochemistry.
First, I am interested in what governs mitochondrial turnover in neuronal synapses. Neuronal mitochondria are important for a number of metabolic, energy-consuming processes that occur in the synapses, including stimulation-dependent exocytosis. Neurons are extremely susceptible to mitochondrial deficiency, which is believed to underlie various neurodegenerative diseases. Mitochondria are subject to anterograde and retrograde transport along the axon; however, what signals synaptic mitochondria to go back to the cell body is poorly understood. While mitochondria are degraded by an autophagic pathway under normal and stress conditions, it is not clear, whether damaged mitochondria are encapsulated into the vacuole at the synapse, or delivered to the cell body prior to degradation. To answer these and other questions,we are developing a transgenic mouse model, in which mitochondria of dopaminergic neurons can be fluorescently labeled in vivo to monitor their movement and life cycle.
Second, I am interested in what regulates mitochondrial transcription using yeast as a model system. Mitochondrial RNA synthesis and degradation are well-balanced in yeast and other eukaryotes, and the transcription process is tightly synchronized with other steps of gene expression, including RNA processing and translation, but the proteins that regulate mitochondrial transcription in this regard are not known to date. Recently, we have identified a DEAD-box helicase that stabilizes mitochondrial transcription complexes in yeast and appears to be important survival under cold stress conditions.
Lastly, my interests include the regulation of catecholamine storage in response to neurostimulants, in particular, how long-term exposure to amphetamines affects vesicular acidity. The proton gradient in the neurotransmitter storage vesicle is a driving force behind the packaging of neurotransmitter into the vesicles against its concentration gradient, and the amount of stored neurotransmitter is proportional to the acidity of the organelle. It has been well established that acute exposure to amphetamines collapses vesicular proton gradient. However, we have recently demonstrated that catecholamine storage vesicles in the chromaffin cells of adrenal glands may undergo hyperacidification and increase their catecholamine content in response to prolonged exposure to methamphetamine. A number of mechanisms that explain this phenomenon have been proposed, including the involvement of a recently discovered biogenic amine-responsive chloride channels whose activity may decrease the electric component of the electrochemical proton gradient, thus allowing more protons to be pumped into the vesicle. I am interested in exploring the mechanism of the drug-induced vesicle acidification using fluorescent labeling and ratiometric measurement of vesicular pH in vivo using C. elegans as a model system.
- Markov DA, Wojtas ID, Tessitore K, Henderson S, McAllister WT. Yeast DEAD box protein Mss116p is a transcription elongation factor that modulates the activity of mitochondrial RNA polymerase. Mol Cell Biol, 34(13): 2360-9, July 2014.
- Markov DA, Savkina M, Anikin M, Del Campo M, Ecker K, Lambowitz AM, De Gnore JP, McAllister WT. Identification of proteins associated with the yeast mitochondrial RNA polymerase by tandem affinity purification. Yeast, 26(8): 423-40, Aug 2009.
- Markov D, Mosharov EV, Setlik W, Gershon MD, Sulzer D. Secretory vesicle rebound hyperacidification and increased quantal size resulting from prolonged methamphetamine exposure. J Neurochem, 107(6): 1709-21, Dec 2008.
- Mosharov EF, Staal RG, Bové J, Prou D, Hananiya A, Markov D, Poulsen N, Larsen KE, Moore CM, Troyer MD, Edwards RH, Przedborski S, Sulter D. Alpha-synuclein overexpression increases cytosolic catecholamine concentration. J Neurosci, 26(36): 9304-11, Sept 2006.
- King, RA, Markov D, Sen R, Weisberg RA, Severinov K. A conserved zinc binding domain in the largest subunit of DNA-dependent RNA polymerase modulates intrinsic transcription termination and antitermination but does not stabilize the elongation complex. J Mol Biol, 342(4): 1143-54, September 2004.
- Markov D, Christie GE, Sauer B, Calendar R, Park T, Young RY, Severinov K. P2 growth restriction on a rpoC mutant is suppressed by alleles of the Rz1 homolog lysC. J Bacteriol, 186(14), 4628-37, July 2004.
- Gruber TM, Markov D, Sharp MM, Young BA, Lu CZ, Zhong HJ, Artsimovitch I, Geszvain KM, Arthur TM, Burgess RR, Landick R, Severinov K, Gross CA. Binding of the initiation factor σ70 to core RNA polymerase is a multi-step process. Mol Cell, 8(1): 21-31, July 2001.
- Markov D, Naryshkina T, Mustaev A, Severinov K. A zinc-binding site in the largest subunit of DNA-dependent RNA polymerase is involved in enzyme assembly. Genes Dev, 13(18): 2439-48, September 1999.
- Nedea EC, Markov D, Naryshkina T, Severinov K. Localization of E. coli rpoC mutations that affect RNA polymerase assembly and activity at high temperature. J Bacteriol, 181(8): 2663-5, April 1999.
- Severinov K, Markov D, Nikiforov V, Severinova E, Landick R, Darst SA, Goldfarb A. Streptolydigin-resistant mutants in an evolutionary conserved region of the β subunit of Escherichia coli RNA polymerase. J Biol Chem, 270(41): 23926-9, October 1995.
(Webpage updated June 2016)