Alexander Galkin, PhD
2001- PhD Biochemistry, Moscow State university
- Assistant Professor of Biophysics (in Pediatrics) at CUMC
Credentials & Experience
Education & Training
- PhD, 2001 Biochemistry, Moscow State University (Russia)
Dr Alexander Galkin's main interests are bioenergetics, mitochondrial metabolism, and research on the role of respiratory chain complexes in pathological conditions such as hypoxia or ischemia/reperfusion.
Where there is oxygen, there is life. In our body energy is generated by mitochondria, often referred to as "powerhouses" of the cell. Most of the oxygen from the air we breathe is consumed by mitochondria to produce energy. This energy is then used for many needs of cells in our bodies such as brain activity, nerve impulse conduction, heart beating, kidney functioning as well as a synthesis of proteins and DNA and much more. Hypoxia or tissue ischemia is the lack of oxygen in any organ, which causes tissue and cell damage because without oxygen energy cannot be produced. Lack of oxygen can be caused by many factors, including pathologies such as stroke in adults, perinatal hypoxia-ischemia in newborns, traumatic brain injury, cardiac arrest and this also occurs during surgery or transplantation. Usually, ischemia is followed by restoration of oxygen supply (reoxygenation), which can make the injury even greater. Mitochondria play a major role in the development of that damage. An enzyme called mitochondrial Complex I is one of the most important and least understood components of the mitochondria and it initiates the processes of energy production during respiration of the cell. Complex I is located at the inner mitochondrial membrane and catalyzes electron transfer from NADH to ubiquinone-10 (Coenzyme Q10) coupled with proton translocation. Dysfunctions of mitochondria and particular of Complex I are involved in many pathological conditions such as Parkinson's disease, various encephalomyopathies , mitochondrially inherited diseases and the process of ageing. Most likely, Complex I is the main generator of deleterious reactive oxygen species (ROS) in the mitochondrial respiratory chain. This enzyme is also a major target during brain and cardiac ischemia/reperfusion injury. We have recently found that Complex I is very important in ischemia/reoxygenation and can be damaged in that process. Its damage results in an energy crisis in a cell, generation of harmful ROS, oxidative stress and eventually leads to tissue injury.
Despite the importance of Complex I in cellular metabolism, little is known about its regulation in vivo. Recently we identified several important ways of Complex I regulation in health and pathology: A/D transition in the heart and brain, the effect of monovalent cations, critical cysteine modification in brain ischemia and flavin loss in stroke and neonatal hypoxic-ischemic injury.
We are always looking for highly motivated undergraduate/graduate students or postdocs. Please contact me directly via e-mail.
- Brain ischemia/reperfusion injury
- Energy metabolism
- Flavin Metabolism
- Galkin A. (2020) Water route for proton pumping in mitochondrial complex I. Nat.Stuct.Mol.Biol. PMID:32826994DOI:10.1038/s41594-020-0500-y
- Niatsetskaya Z, Sosunov S, Stepanova A, Goldman J,Galkin A, Neginskaya M, Pavlov E, Ten V. (2020) Cyclophilin D-dependent oligodendrocyte mitochondrial ion leak contributes to neonatal white matter injury. J.Clin.Invest.PMID:32925170DOI:10.1172/JCI133082
- Schlegel A, Muller X, Mueller M, Stepanova A, Kron P, de Rougemont O, Muiesan P, ClavienPA, Galkin A, Meierhofer D, Dutkowski P. (2020) Hypothermic oxygenated perfusion protects from mitochondrial injury before liver transplantation. EBioMedicine. PMID:32979838 DOI:10.1016/j.ebiom.2020.103014.
- Stepanova A, Galkin A. (2020) Measurement of mitochondrial H2O2 production under varying O2 tensions. Methods in Cell Biology, DOI:org/10.1016/bs.mcb.2019.12.008
- Ten V, and Galkin A. (2019) Mechanism of mitochondrial complex I damage in brain ischemia/reperfusion injury. A hypothesis. Mol Cell Neurosci. 100, 103408. PMID: 31494262 DOI: 10.1016/j.mcn.2019.103408
- Jain IH, Zazzeron L, Goldberger O, Marutani E, Wojtkiewicz GR, Ast T, Wang H, Schleifer G, Stepanova A, Brepoels K, Schoonjans L, Carmeliet P, Galkin A, Ichinose F, Zapol WM, Mootha VK. (2019) Leigh Syndrome Mouse Model Can Be Rescued by Interventions that Normalize Brain Hyperoxia, but Not HIF Activation. Cell Metab. PMID: 31402314, DOI: 10.1016/j.cmet.2019.07.006
- Wojtovich AP, Berry BJ, Galkin A. (2019) Redox Signaling Through Compartmentalization of Reactive Oxygen Species: Implications for Health and Disease. Antioxid Redox Signal.31, 591-593 PMID: 31084372 doi: 10.1089/ars.2019.7804
- Stepanova A, Sosunov S, Niatsetskaya Z, Konrad C, Starkov AA, Manfredi G, Wittig I, Ten V, Galkin A. (2019) Redox-dependent loss of flavin by mitochondrial complex I in brain ischemia/reperfusion injury. Antioxid Redox Signal.31, 608-622. PMID: 31037949
- Stepanova A, Konrad C, Manfredi G, Springett R, Ten V, Galkin A (2019) The dependence of brain mitochondria reactive oxygen species production on oxygen level is linear, except when inhibited by antimycin A. J Neurochem.148, 731-745, DOI: 10.1111/jnc.14654 PMID: 30582748
- Kim M, Stepanova A, Niatsetskaya Z, Sosunov S, Arndt S, Murphy MP, Galkin A, Ten V (2018) Attenuation of oxidative damage by targeting mitochondrial complex I in neonatal hypoxic-ischemic brain injury. Free Radic Biol Med. 124, 517-524. PMID: 30037775.
- Kahl A, Stepanova A, Konrad C, Anderson C, Manfredi G, Zhou P, Iadecola C, Galkin A. (2018) Critical role of flavin and glutathione in Complex I-mediated bioenergetic failure in brain ischemia/reperfusion injury. Stroke. 49, 223-1231.PMID: 29643256
- Sahni PV, Zhang J, Sosunov S, Galkin A, Niatsetskaya Z, Starkov A, Brookes PS, Ten VS. (2018) Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice. Pediatric research.83, 491-497. PMID: 29211056
- Stepanova A, Konrad C, Guerrero-Castillo S, Manfredi G, Vannucci S, Arnold S, Galkin A. (2018) Deactivation of mitochondrial complex I after hypoxia-ischemia in the immature brain. J.Cerebral Blood Flow and Metabolism. 271678X18770331. PMID:29629602
- Sansone P, Savini C, Kurelac I, Chang Q, Amato L, Strillacci A, Stepanova A, Iommarini L, Mastroleo C, Daly L, Galkin A, Thakur B, Soplop N, Uryu K, Hoshino A, Norton L, Bonafe M, Cricca M, Gasparre G, Lyden D, Bromberg J. (2017) Packaging and transfer of mtDNA via exosomes regulate escape from dormancy in hormonal therapy resistant breast cancer Proc Natl Acad Sci U S A, 114:E9066-E9075. PMID: 29073103
- Stepanova, A., Kahl, A., Konrad, C., Ten, V., Starkov, A, Galkin, A. (2017) Reverse electron transfer results in a loss of flavin from mitochondrial complex I. Potential mechanism for brain ischemia/reperfusion injury, J.Cerebral Blood Flow and Metabolism. 271678 X 17730242. PMID:28914132
- Lin H, Magrane J, Rattelle A, Stepanova A, Galkin A, Clark E, Dong Y, M. Halawani S, Lynch D. (2017) Early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in the KIKO mouse model of Friedreich ataxia. Disease Models & Mechanisms,10:1343-1352. PMID:29125827
- Valsecchi F, Konrad C, D'Aurelio M, Ramos-Espiritu LS, Stepanova A, Burstein SR, Galkin A, MagranÃ¨ J, Starkov A, Buck J, Levin LR, Manfredi G. (2017) Distinct intracellular sAC-cAMP domains regulate ER calcium signaling and OXPHOS function. J. Cell. Sci.130:3713-3727. PMID:28864766.
- Kiprowska M.J., Stepanova A., Todaro D.R., Galkin A., Haas A., Wilson S.M., Figueiredo-Pereira M.E. (2017) Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: relevance to Alzheimer's disease. Biochim Biophys Acta., 1863:1157-1170. PMID:28372990
- Galkin A., Moncada S. (2017) Modulation of the conformational state of mitochondrial complex I as a target for therapeutic intervention. Interface Focus, 7:20160104. PMID:28382200
- Stepanova A, Shurubor Y, Valsecchi F, Manfredi G, Galkin A. (2016) Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart. Biochim Biophys Acta.1857:1561-1568. PMID: 27287543
- DrÃ¶se, S., Stepanova A., Galkin A. (2016) Ischemic A/D transition of mitochondrial complex I and its role in ROS generation. Biochim. Biophys. Acta. 1857, 946-957 Hyspler R., Ticha A., Schierbeek H., Galkin A., Zadak Z. (2015) The evaluation and quantitation of dihydrogen metabolism using deuterium isotope in rats. PLoS ONE10:e0130687. PMID:26103048
- Stepanova A., Valls A., Galkin A. (2015) Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex I. Biochim. Biophys. Acta.1847:1085-1092. PMID:26009015
- Babot M., Labarbuta P., Birch A., Kew S., Fuszard M., Botting C., Heide H., Wittig I., Galkin A. (2014) ND3, ND1 and 39 kDa subunits are more exposed in the de-active form of bovine mitochondrial complex I.Biochim. Biophys. Acta.1837:929-939. PMID:24560811
- Babot M., Labarbuta P., Birch A., Galkin A. (2014) Characterisation of the active/deactive transition of mitochondrial complex I. Biochim. Biophys. Acta.1837:1083-1092. PMID:24569053
- Babot M., Galkin A. (2013) Molecular mechanism and physiological role of active-deactive transition of mitochondrial complex I. Biochem. Soc. Trans.41:1325-1330. PMID:24059527
- Ciano M., Fuszard M., Heide H., Botting C.H., Galkin A. (2013) Conformation-specific crosslinking of mitochondrial complex I. FEBS Lett. 587:867-872. PMID:23454639
- Gorenkova N., Robinson E., Grieve D., Galkin A. (2013) Conformational change of mitochondrial complex I increases ROS sensitivity during ischaemia. Antioxid Redox Signal.19, 1459-68. PMID:23419200
- Galkin, A., Abramov, A., Frakich, N., Duchen, M., Moncada, S. (2009) Lack of oxygen deactivates mitochondrial complex I: Implications for ischemic injury? J.Biol.Chem.,284: 36055-36061. PMID:19861410.
- Drose S., Galkin A., Brandt, U. (2009). Measurement of superoxide formation by mitochondrial complex I of Yarrowia lipolytica.Methods in Enzymology456: 475-490. PMID:19348905.
- Galkin, A., Meyer, B., Wittig, I., Karas, M., SchÃ¤gger H., Vinogradov, A., Brandt, U. (2008) Identification of the mitochondrial complex I ND3 subunit as a structural component involved in the active/de-active enzyme transition. J.Biol.Chem.,283: 20907-20913. PMID:18502755.
- Galkin, A. and Moncada, S. (2007 )Nitrosation of mitochondrial complex I. J.Biol.Chem., 282: 37448-37453. PMID:17956863.
- Galkin, A., Higgs, A., Moncada, S. (2007) Nitric oxide and hypoxia. Essays in Biochemistry, 43: 29-40. PMID:17705791.
- Galkin, A., DrÃ¶se, S., Brandt, U. (2006) The proton pumping stoichiometry of purified mitochondrial complex I reconstituted into proteoliposomes. Biochim. Biophys. Acta., 1757:1575-1581. PMID:17094937.
- Galkin, A., Zwicker, K., DrÃ¶se, S., Grgic, L., Kerscher, S. and Brandt, U. (2006) The redox-Bohr group associated with iron-sulfur cluster N2 of complex I. J.Biol.Chem., 281:23013-23017. PMID:16760472.
- DrÃ¶se, S., Galkin, A., Brandt, U. (2005) Proton pumping by complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica reconstituted into proteoliposomes. Biochim. Biophys. Acta., 1710:87-95. PMID:16289468.
- Galkin, A. and Brandt, U. (2005) Superoxide radical formation by pure complex I (NADH: Ubiquinone oxidoreductase) from Yarrowia lipolytica. J.Biol.Chem., 280:30129-30135. PMID:15985426.
- Brandt, U., Abdrakhmanova, A., Zickermann, V., Galkin, A., DrÃ¶se, S., Zwicker, K., Kerscher, S. (2005) Structure-function relationship in mitochondrial complex I of the strictly aerobic yeast Yarrowia lipolytica. Biochem.Soc.Trans., 33:840-844. PMID:16042611.
- Eschemann A., Galkin, A., Oettmeier, W., Brandt, U., Kerscher, S. (2005) HDQ (1-hydroxy-2-dodecyl-4(1H)-quinolone), a high affinity inhibitor for mitochondrial alternative NADH-dehydrogenase - evidence for a ping-pong mechanism. J.Biol.Chem., 280:3138-3142. PMID:15533932.
- Finikova O., Galkin, A., Cordero, M., HÃ¤gerhÃ¤ll, C., Vinogradov, S. (2003) Dendritic porphyrins and tetrabenzoporphyrins: tunable membrane-impermeable fluorescent pH sensors. J.Am.Chem.Soc., 125:4882 - 4893. PMID:12696908.
- Galkin, A., Grivennikova, V.G., Vinogradov, A.D. (1999) Stoichiometry in NADH-quinone reductase reactions catalyzed by the bovine heart submitochondrial particles. FEBS Lett., 451:157-161. PMID:10371157.