A5005302722- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Neuroscience and Neuropharmacology Research
- Cell death mechanisms and regulation
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Traumatic Brain Injury and Neurovascular Disturbances
- Coenzyme Q10 studies and effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Autophagy in Disease and Therapy
- Calpain Protease Function and Regulation
- Metabolism and Genetic Disorders
- Biochemical Acid Research Studies
- Birth, Development, and Health
- Molecular Sensors and Ion Detection
- RNA modifications and cancer
- Fatty Acid Research and Health
- Endoplasmic Reticulum Stress and Disease
- Trace Elements in Health
- Alzheimer's disease research and treatments
- Lipid metabolism and biosynthesis
- Ion channel regulation and function
- S100 Proteins and Annexins
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
University of Maryland, Baltimore
2015-2024
Buck Institute for Research on Aging
2004-2022
VA Maryland Health Care System
2020
Veterans Health Administration
2020
Star Center
2015
Johns Hopkins University
2002-2006
Yale University
2003-2004
Johns Hopkins Medicine
2004
Marine Biological Laboratory
2003
Wake Forest University
2003
The translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus has been implicated in mechanism glutamate excitotoxicity cortical neurons and observed vivo following acute rodent brain injuries. However, time course AIF redistribution is highly controversial. Because elevated intracellular calcium one most ubiquitous features neuronal cell death, this study tested hypothesis that cleavage by calcium-activated protease calpain mediates its release mitochondria. Both...
Maintaining cellular lipid homeostasis is crucial to oxidative tissues, and it becomes compromised in obesity. Lipid droplets (LD) play a central role by mediating fatty acid (FA) storage the form of triglyceride, thereby lowering intracellular levels lipids that mediate lipotoxicity. LDs mitochondria have interconnected functions, anecdotal evidence suggests they physically interact. However, mechanisms interaction not been identified. Perilipins are LD-scaffolding proteins potential...
Abstract Abnormal accumulation of Ca 2+ and exposure to pro‐apoptotic proteins, such as Bax, is believed stimulate mitochondrial generation reactive oxygen species (ROS) contribute neural cell death during acute ischemic traumatic brain injury, in neurodegenerative diseases, e.g. Parkinson's disease. However, the mechanism by which or apoptotic proteins ROS production unclear. We used a sensitive fluorescent probe compare effects on H 2 O emission isolated rat mitochondria presence...
Cultured rat cerebellar granule neurons were incubated with low nanomolar concentrations of the protonophore carbonylcyanide-p-trifluoromethoxyphenyl hydrazone (FCCP) to test hypothesis that 'mild uncoupling' could be neuroprotective by decreasing oxidative stress. To quantify uncoupling, respiration and mitochondrial membrane potential (Deltapsi(m)) determined in parallel as a function FCCP concentration. Deltapsi(m) dropped less than 10 mV before respiratory control was lost. Conditions...
Previous studies using in vitro cell culture systems have shown the role of dynamin-related GTPase Opa1 apoptosis prevention and mitochondrial DNA (mtDNA) maintenance. However, it remains to be tested whether these functions are physiologically important vivo mammals. Here, Cre-loxP system, we deleted mouse pancreatic beta cells, which glucose-stimulated ATP production mitochondria plays a key insulin secretion. Beta cells lacking maintained normal copy numbers mtDNA; however, amount...
Ubiquitin- and proteasome-dependent outer mitochondrial membrane (OMM)-associated degradation (OMMAD) is critical for cellular homeostasis. However, the scope molecular mechanisms of OMMAD pathways are still not well understood. We report that OMM-associated E3 ubiquitin ligase MARCH5 controls dynamin-related protein 1 (Drp1)-dependent fission cell sensitivity to stress-induced apoptosis. knockout selectively inhibited ubiquitination proteasomal MiD49, a receptor Drp1, consequently led...
The BH3 domain is essential for the release of cytochrome c from mitochondria by pro-apoptotic Bcl-2 family proteins during apoptosis. This study tested hypothesis that a Bax peptide includes can permeabilize mitochondrial outer membrane and in absence permeability transition at inner membrane. (0.1-60 microm) released presence physiological concentrations ions cell type-selective manner, whereas with single amino acid substitution was ineffective. correlated endogenous its integral...
Mitochondria can depolarize and trigger cell death through the opening of mitochondrial permeability transition pore (MPTP). We recently showed that an increase in long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) depletion n6 PUFA arachidonic (ARA; 20:4n6) membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated phospholipid composition by supplementing diet DHA, ARA or combined DHA+ARA rats for 10 weeks. There...
Activation of genes promoting aerobic glycolysis and suppression mitochondrial oxidative phosphorylation is one the hallmarks cancer. The RUNX2 transcription factor mediates breast cancer (BC) metastasis to bone regulated by glucose availability. But, mechanisms which it regulates metabolism promotes an oncogenic phenotype are not known. expression in luminal BC cells correlated with lower estrogen receptor-α (ERα) levels, anchorage-independent growth, glycolytic genes, increased uptake,...
Transient global ischemia is a neuronal insult that induces delayed cell death. A hallmark event in the early post-ischemic period enhanced permeability of mitochondrial membranes. The precise mechanisms by which function disrupted are, as yet, unclear. Here we show promotes alterations membrane contact points, rise intramitochondrial Zn<sup>2+</sup>, and activation large, multi-conductance channels outer membranes 1 h after insult. Mitochondrial channel activity was associated with protease...
BCL-2 family proteins are known to regulate cell death during development by influencing the permeability of mitochondrial membranes. The anti-apoptotic protein BCL-xL is highly expressed in adult brain and localizes mitochondria presynaptic terminal squid stellate ganglion. Application recombinant through a patch pipette inside giant triggered multiconductance channel activity Furthermore, injection full-length into enhanced postsynaptic responses rate recovery from synaptic depression,...
Neuronal death is often preceded by functional alterations at nerve terminals. Anti- and proapoptotic BCL-2 family proteins not only regulate the neuronal pathway but also affect excitability of healthy neurons. We found that exposure squid stellate ganglia to hypoxia, a stimulus for neurons, causes cysteine protease-dependent loss full-length antiapoptotic BCL-xL, similar previous findings in mammalian cells. Therefore, determine direct effect naturally occurring cleavage product BCL-xL on...