A5023494464- Heme Oxygenase-1 and Carbon Monoxide
- Hemoglobin structure and function
- Sulfur Compounds in Biology
- Porphyrin Metabolism and Disorders
- Neonatal Health and Biochemistry
- Alcohol Consumption and Health Effects
- Neuroscience of respiration and sleep
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Erythrocyte Function and Pathophysiology
- Photosynthetic Processes and Mechanisms
- Coenzyme Q10 studies and effects
- Odor and Emission Control Technologies
- Adipose Tissue and Metabolism
- Cannabis and Cannabinoid Research
- Advanced battery technologies research
- Burn Injury Management and Outcomes
- Nitric Oxide and Endothelin Effects
- Mitochondrial Function and Pathology
- Eicosanoids and Hypertension Pharmacology
- Protein Degradation and Inhibitors
- Genetics and Neurodevelopmental Disorders
Michigan Medicine
2021-2025
University of Michigan
2022-2024
Georgia Institute of Technology
2016-2024
Parker Hannifin (United States)
2024
AID Atlanta
2022
Significance All heme-dependent functions require the mobilization of labile heme (LH), which there is little understanding its nature and dynamics. To probe LH pools, we developed genetically encoded fluorescent sensors deployed them in unicellular eukaryote Saccharomyces cerevisiae . We find that relatively abundant cytosol, but exceedingly low mitochondria nucleus. Further, can be mobilized by signaling molecules like nitric oxide. also glycolytic enzyme glyceraldehyde phosphate...
Heme is an essential prosthetic group in proteins that reside virtually every subcellular compartment performing diverse biological functions. Irrespective of whether heme synthesized the mitochondria or imported from environment, this hydrophobic and potentially toxic metalloporphyrin has to be trafficked across membrane barriers, a concept heretofore poorly understood. Here we show, using subcellular-targeted, genetically encoded hemoprotein peroxidase reporters, both extracellular...
Heme (iron protoporphyrin IX) is an essential protein prosthetic group and signaling molecule required for most life on Earth. All heme-dependent processes require the dynamic rapid mobilization of heme from sites synthesis or uptake to hemoproteins present in virtually every subcellular compartment. The cytotoxicity hydrophobicity necessitate that be carefully controlled mitigate deleterious effects this toxin. Indeed, a number disorders, including certain cancers, cardiovascular diseases,...
Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism mammals. At a cellular level, H 2 S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, durability of these changes is unknown. We report that despite its volatility, preconditioning increases P 50(O2) , O pressure for half-maximal respiration, has pleiotropic effects on oxidative metabolism...
Protoheme (hereafter referred to as heme) is an essential cellular cofactor and signaling molecule that also potentially cytotoxic. To mitigate heme toxicity, synthesis degradation are tightly coupled utilization in order limit the intracellular concentration of "free" heme. Such a model, however, would suggest readily accessible steady-state, bioavailable labile (LH) pool not required for supporting heme-dependent processes. Using yeast Saccharomyces cerevisiae model fluorescent sensors,...
Mammalian cells synthesize H2S from sulfur-containing amino acids and are also exposed to exogenous sources of this signaling molecule, notably gut microbes. As an inhibitor complex IV in the electron transport chain, can have a profound impact on metabolism, suggesting hypothesis that metabolic reprogramming is primary mechanism by which signals. In study, we report increases lipogenesis many cell types, using carbon derived glutamine rather than glucose. H2S-stimulated lipid synthesis...
Abstract Heme b (iron protoporphyrin IX) plays important roles in biology as a metallocofactor and signaling molecule. However, the targets of heme network proteins that mediate exchange from sites synthesis or uptake to dependent regulated are poorly understood. Herein, we describe quantitative mass spectrometry (MS)-based chemoproteomics strategy identify labile hemoproteins human embryonic kidney HEK293 cells may be relevant trafficking. The involves depleting endogenous with biosynthetic...
Inter-organellar communication is critical for cellular metabolic homeostasis. One of the most abundant inter-organellar interactions are those at endoplasmic reticulum and mitochondria contact sites (ERMCS). However, a detailed understanding mechanisms governing ERMCS regulation their roles in metabolism limited by lack tools that permit temporal induction reversal. Through unbiased screening approaches, we identified fedratinib, an FDA-approved drug, dramatically increases abundance...
Ubiquinol or coenzyme Q (CoQ) is a lipid-soluble electron carrier in the respiratory chain and an acceptor for various enzymes metabolic pathways that intersect at this cofactor hub mitochondrial inner membrane. The reduced form of CoQ antioxidant, which protects against lipid peroxidation. In study, we have optimized UV-detected HPLC method analysis from biological materials, involves rapid single-step extraction into n-propanol followed by direct sample injection onto column. Using method,...
Heme oxygenases (HOs) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin excreted. Humans express two isoforms of HO: the inducible HO-1, upregulated in response excess other stressors, constitutive HO-2. Much known about regulation physiological function whereas comparatively little role HO-2 regulating homeostasis. The biochemical necessity for expressing dependent on whether sufficiently abundant accessible as a substrate...
Abstract Mitochondrial form and function are intimately interconnected, responding to cellular stresses changes in energy demand. Hydrogen sulfide, a product of amino acid metabolism, has dual roles as an electron transport chain substrate complex IV (CIV) inhibitor, leading reductive shift, which pleiotropic metabolic consequences. Luminal sulfide concentration colon is high due microbial activity, this study, we demonstrate that chronic exposure colonocyte-derived cells leads lower Mic60...
ABSTRACT Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism mammals. At a cellular level, H 2 S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, durability of these changes is unknown. We report that despite its volatility, preconditioning increases P 50(O2) , O pressure for half maximal respiration, has pleiotropic effects on oxidative...
Abstract Heme b (iron protoporphyrin IX) plays important roles in biology as a metallocofactor and signaling molecule. However, the targets of heme network proteins that mediate exchange from sites synthesis or uptake to dependent regulated are poorly understood. Herein, we describe quantitative mass spectrometry-based chemoproteomics strategy identify labile hemoproteins human embryonic kidney HEK293 cells may be relevant trafficking. The involves depleting endogenous with biosynthetic...
Abstract Heme oxygenases (HO) detoxify heme by oxidatively degrading it into carbon monoxide, iron, and biliverdin, which is reduced to bilirubin excreted. Humans express two isoforms: inducible HO-1, up-regulated in response various stressors, including excess heme, constitutive HO-2. While much known about the regulation physiological function of comparatively little role HO-2 regulating homeostasis. The biochemical necessity for expressing largely dependent on whether sufficiently...