Biology subjects

Munger, J.

Publications and source records attributed to Munger, J..

3 recordsLinked to original sources

bioRxiv2018

The Portal Project: a long-term study of a Chihuahuan desert ecosystem

This is a data paper for the Portal Project, a long-term ecological study of rodents, plants, and ants located in southeastern Arizona, U.S.A. This paper contains an overview of methods and information about the structure of the data files and the relational structure among the files. This is a living data paper and will be updated with new information as major changes or additions are made to the data. All data - along with more detailed data collection protocols and site information - is archived at: https://doi.org/10.5281/zenodo.1215988.

ecology↗

bioRxiv2017

Nicotinamide mononucleotide (NMN) affords cardioprotection by stimulating glycolysis

Stimulation of the cytosolic NAD+ dependent deacetylase SIRT1 is cardioprotective against ischemia-reperfusion (IR) injury. NAD+ precursors including nicotinamide mononucleotide (NMN) are thought to induce cardioprotection via SIRT1. Herein, while NMN protected perfused hearts against IR (functional recovery: NMN 42{+/-}7% vs. vehicle 11{+/-}3%), this protection was insensitive to the SIRT1 inhibitor splitomicin (recovery 47{+/-}8%). Although NMN-induced cardioprotection was absent in Sirt3-/- hearts (recovery 9{+/-}5%), this was likely due to enhanced baseline injury in Sirt3-/- (recovery 6{+/-}2%), since similar injury levels in WT hearts also blunted the protective efficacy of NMN. Considering alternative cardiac effects of NMN, and the requirement of glycolysis for NAD+, we hypothesized NMN may confer protection via direct stimulation of cardiac glycolysis. In primary cardiomyocytes, NMN induced cytosolic and extracellular acidification and elevated lactate. In addition, [U-13C]glucose tracing in intact hearts revealed that NMN stimulated glycolytic flux. Consistent with a role for glycolysis in NMN-induced protection, hearts perfused without glucose (palmitate as fuel source), or hearts perfused with galactose (no ATP from glycolysis) exhibited no benefit from NMN (recovery 11{+/-}4% and 15{+/-}2% respectively). Acidosis during early reperfusion is known to be cardioprotective (i.e., acid post-conditioning), and we also found that NMN was cardioprotective when delivered acutely at reperfusion (recovery 39{+/-}8%). This effect of NMN was not additive with acidosis, suggesting overlapping mechanisms. We conclude that the acute cardioprotective benefits of NMN are mediated via glycolytic stimulation, with the downstream protective mechanism involving enhanced ATP synthesis during ischemia and/or enhanced acidosis during reperfusion.

biochemistry↗

bioRxiv2017

Potential Mechanisms Linking SIRT Activity And Hypoxic 2-Hydroxyglutarate Generation: No Role For Direct Enzyme (De)acetylation

2-hydroxyglutarate (2-HG) is a hypoxic metabolite with potentially important epigenetic signaling roles. The mechanisms underlying 2-HG generation are poorly understood, but evidence suggests a potential regulatory role for the sirtuin family of lysine deacetylases. Thus, we hypothesized that the acetylation status of the major 2-HG-generating enzymes (isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH) and lactate dehydrogenase (LDH)) may govern their 2-HG generating activity. In-vitro acetylation of these enzymes, with confirmation by western blotting, mass spectrometry, and reversibility by incubation with recombinant sirtuins, yielded no effect on 2-HG generating activity. In addition, while elevated 2-HG in hypoxia is associated with the activation of lysine deacetylases, we found that mice lacking mitochondrial SIRT3 exhibited hyperacetylation and elevated 2-HG. These data suggest there is no direct link between enzyme acetylation and 2-HG production. Furthermore, our observed effects of in-vitro acetylation on the canonical activities of IDH, MDH and LDH appeared to contrast sharply with previous findings wherein acetyl-mimetic lysine mutations resulted in inhibition of these enzymes. Overall these data suggest that a causal relationship should not be assumed, between acetylation of metabolic enzymes and their activities, canonical or otherwise.

biochemistry↗