A5013687539- Mitochondrial Function and Pathology
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Muscle metabolism and nutrition
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Biochemical Acid Research Studies
- ATP Synthase and ATPases Research
- Research Data Management Practices
- Immune Cell Function and Interaction
- Neuroscience of respiration and sleep
- Electron and X-Ray Spectroscopy Techniques
- Immune cells in cancer
- Lipid metabolism and biosynthesis
- Ion channel regulation and function
- Fungal and yeast genetics research
- Advanced Materials Characterization Techniques
- HVDC Systems and Fault Protection
- Heme Oxygenase-1 and Carbon Monoxide
- Biomedical Text Mining and Ontologies
- Advanced biosensing and bioanalysis techniques
- Cardiac Structural Anomalies and Repair
University of Utah
2019-2024
Howard Hughes Medical Institute
2018-2023
Cardiff University
2021
Whitehead Institute for Biomedical Research
2018-2019
Massachusetts Institute of Technology
2018
National Institute of Biomedical Imaging and Bioengineering
2012
National Institutes of Health
2012
University of Michigan–Ann Arbor
2010
Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by synthase, FASN) and mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially higher eukaryotes, with major product(s), metabolic roles, cellular function(s) being essentially unknown. Here we show that hypomorphic mutant mouse skeletal myoblast cell lines display a severe loss of electron transport chain (ETC) complexes exhibit compensatory activities including reductive...
Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in inner mitochondrial membrane (IMM), where it dissipates potential independent adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose...
Abstract Despite the vast number of modification sites mapped within mRNAs, known examples consequential mRNA modifications remain rare. Here, we provide multiple lines evidence to show that Ime4p, an N 6-methyladenosine (m 6 A) methyltransferase required for meiosis in yeast, acts by methylating a site 3′ UTR encoding Rme1p, transcriptional repressor meiosis. Consistent with this mechanism, genetic analyses reveal IME4 functions upstream RME1 . Transcriptome-wide, is primary message...
Peroxisomal biogenesis disorders (PBDs) are genetic of peroxisome and metabolism that characterized by profound developmental neurological phenotypes. The most severe class PBDs—Zellweger spectrum disorder (ZSD)—is caused mutations in peroxin genes result both non‐functional peroxisomes mitochondrial dysfunction. It is unclear, however, how defective contribute to impairment. In order understand the molecular basis this inter‐organellar relationship, we investigated fate peroxisomal mRNAs...
Gold nanoparticles (AuNPs) with core sizes below 2 nm and compact ligand shells constitute versatile platforms for the development of novel reagents in nanomedicine. Due to their ultrasmall size, these AuNPs are especially attractive applications requiring delivery crowded intracellular spaces cytosol nucleus. For eventual use vivo, should ideally be monodisperse, since small variations size may affect how they interact cells behave body. Here we report synthesis ultrasmall, uniform 144-atom...
The fate of pyruvate is a defining feature in many cell types. One major mitochondrial entry via the carrier (MPC). We found that diffuse large B lymphomas (DLBCLs) consume glutamate-pyruvate transaminase 2 to enable α-ketoglutarate production as part glutaminolysis. This led us discover glutamine exceeds carbon source for tricarboxylic acid cycle DLBCLs. As result, MPC inhibition decreased glutaminolysis DLBCLs, opposite previous observations other also or genetic depletion DLBCL...
Ribosome profiling, an application of nucleic acid sequencing for monitoring ribosome activity, has revolutionized our understanding protein translation dynamics. This technique been available a decade, yet the current state and standardization publicly computational tools these data is bleak. We introduce XPRESSyourself, analytical toolkit that eliminates barriers bottlenecks associated with this specialized type by filling gaps in toolset both experts non-experts profiling. XPRESSyourself...
Abstract Lactate is the highest turnover circulating metabolite in mammals. While traditionally viewed as a waste product, lactate an important energy source for many organs, but first must be oxidized to pyruvate entry into tricarboxylic acid cycle (TCA cycle). This reaction thought occur cytosol, with subsequently transported mitochondria via mitochondrial carrier (MPC). Using 13 C stable isotope tracing, we demonstrated that myocardial tissue of mice even when MPC genetically deleted....
Abstract Spliceosomal introns are ubiquitous non-coding RNAs typically destined for rapid debranching and degradation. Here, we describe 34 excised Saccharomyces cerevisiae that, although rapidly degraded in log-phase growth, accumulate as linear under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, a key integrator growth signaling. Introns become stabilized remain associated with components the spliceosome differ from spliceosomal having short...
Abstract Ribosome profiling, an application of nucleic acid sequencing for monitoring ribosome activity, has revolutionized our understanding protein translation dynamics. This technique been available a decade, yet the current state and standardization publicly computational tools these data is bleak. We introduce XPRESSyourself, analytical toolkit that eliminates barriers bottlenecks associated with this specialized type by filling gaps in toolset both experts non-experts profiling....
Abstract Peroxisomal Biogenesis Disorders (PBDs) are a class of inherited metabolic disorders with profound neurological and other phenotypes. The most severe PBDs caused by mutations in peroxin genes, which result nonfunctional peroxisomes typically through impaired protein import. In order to better understand the molecular causes Zellweger Spectrum Disease (ZSD) -the -, we investigated fate peroxisomal mRNAs proteins ZSD model systems. We found that loss import has no effect on mRNA...
Extended abstract of a paper presented at Microscopy and Microanalysis 2012 in Phoenix, Arizona, USA, July 29 – August 2, 2012.
Mitochondria are often dubbed “the powerhouse of the cell,” however this gross over‐simplification has arguably led to a paucity knowledge concerning many other functions these incredibly diverse organelles. Fatty acid synthesis (FAS) is an essential cellular process, but it little‐known fact even among mitochondrial experts that eukaryotes actually harbor two distinct FAS systems – one in cytoplasm, and mitochondria. Although (mtFAS) was discovered decades ago, its function(s) mammals still...
Abstract Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by synthase, FASN) and mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially higher eukaryotes, with major product(s), metabolic roles, cellular function(s) being essentially unknown. Here we show that hypomorphic mutants display a severe loss of electron transport chain (ETC) complexes exhibit compensatory activities including reductive carboxylation. This effect on ETC...
SUMMARY Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in inner mitochondrial membrane (IMM), where it dissipates potential independent ATP synthase. Here we provide evidence that phosphatidylethanolamine (PE) directly regulates UCP1-dependent proton conductance across IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance...
SUMMARY The fate of pyruvate, which is modulated by the activity mitochondrial pyruvate carrier (MPC), a defining metabolic feature in many cancers. Diffuse large B-cell lymphomas (DLBCLs) are genetically and metabolically heterogeneous cancer. Although MPC expression differed between DLBCL subgroups, was uniformly consumed glutamate transaminase 2 (GPT2) to support α-ketoglutarate production as part glutaminolysis. This led us discover that glutamine exceeds carbon source for tricarboxylic...