A5036417376- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- ATP Synthase and ATPases Research
- Microbial Metabolic Engineering and Bioproduction
- Cardiac electrophysiology and arrhythmias
- Cardiac Ischemia and Reperfusion
- Photoreceptor and optogenetics research
- Electron Spin Resonance Studies
- Cardiovascular Function and Risk Factors
- Protein Structure and Dynamics
- Gene Regulatory Network Analysis
- Diet and metabolism studies
- Photosynthetic Processes and Mechanisms
- Plant and Biological Electrophysiology Studies
- Redox biology and oxidative stress
- Metabolomics and Mass Spectrometry Studies
- Fuel Cells and Related Materials
- Fungal and yeast genetics research
- Dietary Effects on Health
- thermodynamics and calorimetric analyses
- Bioinformatics and Genomic Networks
- Genetics, Aging, and Longevity in Model Organisms
- Cardiomyopathy and Myosin Studies
- Circadian rhythm and melatonin
- Ion channel regulation and function
National Institute on Aging
2016-2024
National Institutes of Health
2016-2023
Institute on Aging
2018-2022
Johns Hopkins University
2009-2018
Johns Hopkins Medicine
2009-2018
Government of the United States of America
2018
Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine
2014
Zhejiang University
2014
Cornell University
2007
Saarland University
2006
Reactive oxygen species (ROS) and/or Ca2+ overload can trigger depolarization of mitochondrial inner membrane potential (ΔΨm) and cell injury. Little is known about how loss ΔΨm in a small number mitochondria might influence the overall function cell. Here we employ narrow focal excitation volume two-photon microscope to examine effect local guinea pig ventricular myocytes. Remarkably, single laser flash triggered synchronized self-sustained oscillations ΔΨm, NADH, ROS after delay ∼40s, more...
Abstract To characterize the proteomic signature of chronological age, 1,301 proteins were measured in plasma using SOMAscan assay (SomaLogic, Boulder, CO, USA) a population 240 healthy men and women, 22–93 years old, who disease‐ treatment‐free had no physical cognitive impairment. Using p ≤ 3.83 × 10 −5 significance threshold, 197 positively associated, 20 negatively associated with age. Growth differentiation factor 15 (GDF15) strongest, positive association age (GDF15; 0.018 ± 0.001, =...
Mitochondrial Ca 2+ ([Ca ] m ) regulates oxidative phosphorylation and thus contributes to energy supply demand matching in cardiac myocytes. Mitochondria take up via the uniporter (MCU) extrude it through mitochondrial Na + /Ca exchanger (mNCE). It is controversial whether mitochondria rapidly, on a beat-to-beat basis, or slowly, by temporally integrating cytosolic c transients. Furthermore, although efflux governed mNCE, unknown elevated intracellular ([Na i affects uptake bioenergetics....
Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging metabolism through mechanisms that largely remain unknown. Here, we show overexpression reduction frailty lifespan extension both male female B6 mice. A combination of physiological assays, vivo multi-omics analyses 13C lactate tracing identified an age-dependent glucose homeostasis hepatic output wild type In contrast, aged SIRT6-transgenic mice preserve...
Recovery of the mitochondrial inner membrane potential (ΔΨm) is a key determinant postischemic functional recovery heart. Mitochondrial ROS-induced ROS release causes collapse ΔΨm and destabilization action (AP) through mechanism involving anion channel (IMAC) modulated by benzodiazepine receptor (mBzR). Here, we test hypothesis that this contributes to spatiotemporal heterogeneity during ischemia-reperfusion (IR), thereby promoting abnormal electrical activation arrhythmias in whole...
Skeletal myoblasts are an attractive cell type for transplantation because they autologous and resistant to ischemia. However, clinical trials of myoblast in heart failure have been plagued by ventricular tachyarrhythmias sudden cardiac death. The pathogenesis these arrhythmias is poorly understood, but may be related the fact that skeletal muscle cells, unlike electrically isolated absence gap junctions. Using a novel vitro model cardiomyocyte monolayers, we investigated mechanisms...
Synchronization of mitochondrial function is an important determinant cell physiology and survival, yet little known about the mechanism interorganellar communication. We have recently observed that coordinated cell-wide oscillations in energy state heart cells can be induced by a highly localized perturbation few elements network, indicating mitochondria represent complex, self-organized system. Here, we apply percolation theory to explain intermitochondrial signal propagation response...
Heart failure remains a leading cause of morbidity and mortality worldwide. Although depressed pump function is common, development effective therapies to stimulate contraction has proven difficult. This thought be attributable their frequent reliance on cAMP stimulation increase activator Ca 2+ . A potential alternative nitroxyl (HNO), the 1-electron reduction product nitric oxide (NO) that improves relaxation in normal failing hearts vivo. The mechanism for myocyte effects unknown. Here,...
Mammalian Bcl-xL protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced membrane permeabilization. Contrary expectation, we found electron microscopy biochemical approaches that endogenous also localized inner cristae. Two-photon of cultured neurons revealed large fluctuations in potential when was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into out mitochondria. Computational,...
The net emission of hydrogen peroxide (H2O2) from mitochondria results the balance between reactive oxygen species (ROS) continuously generated in respiratory chain and ROS scavenging. relative contribution two major antioxidant systems mitochondrial matrix, glutathione (GSH) thioredoxin (Trx), has not been assessed. In this paper, we examine key question via combined experimental theoretical approaches, using isolated heart mouse, rat, guinea pig. As compared with untreated control...
Respiring mitochondria produce H(2)O(2) continuously. When production exceeds scavenging, emission occurs, endangering cell functions. The mitochondrial peroxidase peroxiredoxin-3 reduces to water using reducing equivalents from NADPH supplied by thioredoxin-2 (Trx2) and, ultimately, thioredoxin reductase-2 (TrxR2). Here, the contribution of this system control was studied in isolated and cardiomyocytes mouse or guinea pig heart. Energization addition glutamate/malate resulted a 10-fold...
Loss of mitochondrial function is a fundamental determinant cell injury and death. In heart cells under metabolic stress, we have previously described how the abrupt collapse or oscillation energy state synchronized across network by local interactions dependent upon reactive oxygen species (ROS). Here, develop mathematical model ROS-induced ROS release (RIRR) based on reaction-diffusion (RD-RIRR) in one- two-dimensional networks. The nodes RD-RIRR are comprised models individual...