A5012679408- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Adipose Tissue and Metabolism
- Photosynthetic Processes and Mechanisms
- Nitric Oxide and Endothelin Effects
- Metabolomics and Mass Spectrometry Studies
- Neonatal and fetal brain pathology
- Neurological Disease Mechanisms and Treatments
- Cardiac Ischemia and Reperfusion
- Amyotrophic Lateral Sclerosis Research
- Metalloenzymes and iron-sulfur proteins
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Anesthesia and Neurotoxicity Research
- Genetic Neurodegenerative Diseases
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Neurological Disorders and Treatments
- Electron Spin Resonance Studies
- Electrochemical Analysis and Applications
- Organ Transplantation Techniques and Outcomes
- Liver Disease and Transplantation
- Microbial Metabolic Engineering and Bioproduction
- Ubiquitin and proteasome pathways
Cornell University
2016-2025
MIND Research Institute
2016-2025
Columbia University
2018-2024
Weill Cornell Medicine
2016-2024
Columbia University Irving Medical Center
2021-2022
City Hospital № 1 named after. ON. Semashko
2020
Central Clinical Hospital No 2 named Semashko
2019
Queen's University Belfast
2010-2018
City Hospital No. 40
2016
Goethe University Frankfurt
2004-2012
Significance Increasing evidence suggests that extracellular vesicles (EVs) can transfer genetic material to recipient cells. However, the mechanism and role of this phenomenon are largely unknown. Here we have made a remarkable discovery: EVs harbor full mitochondrial genome. These in turn their mtDNA cells with impaired metabolism, leading restoration metabolic activity. We determined hormonal therapy induces oxidative phosphorylation-deficient breast cancer cells, which be rescued via...
BackgroundMitochondrial succinate accumulation has been suggested as key event for ischemia reperfusion injury in mice. No specific data are however available on behavior of liver mitochondria during ex situ machine perfusion clinical transplant models.MethodsWe investigated mitochondrial metabolism isolated perfused rat livers before transplantation. Livers were exposed to warm and cold simulate donation after circulatory death (DCD) organ transport. Subsequently, with oxygenated Belzer-MPS...
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here this impairment crosstalk between mitochondria and ER impedes use glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids sustain energy production. Over time, deficiency alters electron flow active/dormant status complex I spinal cord tissues,...
We explored the transformations accompanying transmission of odor information from first-order processing area, antennal lobe, to mushroom body, a higher-order integration center in insect brain. Using Ca2+ imaging, we recorded activity dendrites projection neurons that connect lobe with body. Next, presynaptic terminals these neurons. Finally, characterized their postsynaptic partners, intrinsic clawed Kenyon cells. found fundamental differences coding between and Odors evoked combinatorial...
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) undergoes reversible deactivation upon incubation at 30-37 degrees C. The active/deactive transition could play an important role in the regulation of activity. It has been suggested recently that may become modified by S-nitrosation under pathological conditions during hypoxia or when nitric oxide:oxygen ratio increases. Apparently, a specific cysteine becomes accessible to chemical modification only deactive form enzyme. By selective...
Tightly coupled bovine heart submitochondrial particles treated to activate complex I and block ubiquinol oxidation were capable of rapid uncoupler‐sensitive inside‐directed proton translocation when a limited amount NADH was oxidized by the exogenous ubiquinone homologue Q 1 . External alkalization, internal acidification followed rapidly responding ( t 1/2 ≤1 s) spectrophotometric technique. Quantitation initial rates external H + decrease resulted in stoichiometric ratio 4 vectorially...
Generation of reactive oxygen species (ROS) is increasingly recognized as an important cellular process involved in numerous physiological and pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) considered one the major sources ROS within mitochondria. Yet, exact site mechanism superoxide production by this large membrane-bound multiprotein complex has remained controversial. Here we show that isolated from Yarrowia lipolytica forms at a rate 0.15% measured for catalytic...
The pH dependencies of the UV−vis and fluorescent spectra new water-soluble dendritic porphyrins tetrabenzoporphyrins were studied. Because extended π-conjugation nonplanar distortion, absorption emission bands tetraaryltetrabenzoporphyrins (Ar4TBP) are red-shifted do not overlap with those regular tetraarylporphyrins (Ar4P). When encapsulated inside dendrimers hydrophilic outer layers, Ar4Ps Ar4TBPs become water soluble can serve as indicators, pK's adjustable by peripheral charges on...
For S-nitrosothiols and peroxynitrite to interfere with the activity of mitochondrial complex I, prior transition enzyme from its active (A) deactive, dormant (D) state is necessary. We now demonstrate accumulation D-form I in human epithelial kidney cells after prolonged hypoxia. Upon reoxygenation hypoxia there was an initial delay return respiration rate normal. This due slow, substrate-dependent reconversion A-form. Reconversion A-form could be prevented by incubation endogenously...
Nitric oxide is known to cause persistent inhibition of mitochondrial respiration as a result S-nitrosation NADH: ubiquinone oxidoreductase (complex I) (Clementi, E., Brown, G. C., Feelisch, M., and Moncada, S. (1998) Proc. Natl. Acad. Sci. U. A. 95, 7631–7636). Little about whether such nitrosation occurs in physiological conditions and, if so, what are the possible cellular mechanisms. We have now found that conformational state (active/deactive transition (Vinogradov, D. Biochim. Biophys....
Aims: Myocardial ischemia/reperfusion (I/R) is associated with mitochondrial dysfunction and subsequent cardiomyocyte death. The generation of excessive quantities reactive oxygen species (ROS) resultant damage to enzymes considered an important mechanism underlying reperfusion injury. Mitochondrial complex I can exist in two interconvertible states: active (A) deactive or dormant (D). We have studied the active/deactive (A/D) equilibrium several tissues under ischemic conditions vivo...
Background and Purpose— Ischemic brain injury is characterized by 2 temporally distinct but interrelated phases: ischemia (primary energy failure) reperfusion (secondary failure). Loss of cerebral blood flow leads to decreased oxygen levels crisis in the ischemic area, initiating a sequence pathophysiological events that after reoxygenation lead ischemia/reperfusion (I/R) damage. Mitochondrial impairment oxidative stress are known be early I/R injury. However, biochemical mechanisms...
Aims: Brain ischemia/reperfusion (I/R) is associated with impairment of mitochondrial function. However, the mechanisms failure are not fully understood. This work was undertaken to determine and time course energy dysfunction after reperfusion following neonatal brain hypoxia-ischemia (HI) in mice. Results: HI/reperfusion decreased activity complex I, which recovered 30 min then declined again 1 h. Decreased I occurred parallel a loss content noncovalently bound membrane flavin...
Abstract Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder without cure. Here we show that mitochondrial respiratory chain complex I an important small molecule druggable target in AD. Partial inhibition of triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection symptomatic APP/PS1 female mice, translational model Treatment mice with inhibitor improved energy homeostasis, synaptic activity, long-term potentiation, dendritic spine...
ABSTRACT Friedreich ataxia (FRDA), the most common recessive inherited ataxia, results from deficiency of frataxin, a small mitochondrial protein crucial for iron-sulphur cluster formation and ATP production. Frataxin is associated with dysfunction in FRDA patients animal models; however, early pathology cerebellum remains elusive. Using frataxin knock-in/knockout (KIKO) mice KIKO carrying mitoDendra transgene, we show cerebellar deficits biogenesis respiratory chain complexes this model. At...
Establishing sustained reoxygenation/reperfusion ensures not only the recovery, but may initiate a reperfusion injury in which oxidative stress plays major role. This study offers mechanism and this mechanism-specific therapeutic strategy against excessive release of reactive oxygen species (ROS) associated with reperfusion-driven recovery mitochondrial metabolism. In neonatal mice subjected to cerebral hypoxia-ischaemia (HI) reperfusion, we examined conformational changes activity complex I...
Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and electron transport chain. Studies of complex are clinically important since new roles for this have recently emerged in cell signalling, cancer biology, immune response neurodegeneration. Oxaloacetate (OAA) an intermediate TCA at same time inhibitor with high affinity (Kd~10(-8)M). Whether or not OAA inhibition physiologically relevant process significant, but still controversial topic....
Ischemic stroke is one of the most prevalent sources disability in world. The major brain tissue damage takes place upon reperfusion ischemic tissue. Energy failure due to alterations mitochondrial metabolism and elevated production reactive oxygen species (ROS) main causes ischemia-reperfusion (IR) damage. Ischemia resulted accumulation succinate tissues, which favors process reverse electron transfer (RET) when a fraction electrons derived from directed complex I for reduction matrix NAD +...
Proton pumping respiratory complex I (NADH:ubiquinone oxidoreductase) is a major component of the oxidative phosphorylation system in mitochondria and many bacteria. In mammalian cells it provides 40% proton motive force needed to make ATP. Defects this giant most complicated membrane-bound enzyme cause numerous human disorders. Yet mechanism still elusive. A group exhibiting redox-linked protonation that associated with iron-sulfur cluster N2 has been proposed act as central machinery. Here...