scholarly journals Nuclear NAD+-biosynthetic enzyme NMNAT1 facilitates development and early survival of retinal neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
David Sokolov ◽  
Emily R Sechrest ◽  
Yekai Wang ◽  
Connor Nevin ◽  
Jianhai Du ◽  
...  

Despite mounting evidence that the mammalian retina is exceptionally reliant on proper NAD+ homeostasis for health and function, the specific roles of subcellular NAD+ pools in retinal development, maintenance, and disease remain obscure. Here, we show that deletion of the nuclear-localized NAD+ synthase nicotinamide mononucleotide adenylyltransferase-1 (NMNAT1) in the developing murine retina causes early and severe degeneration of photoreceptors and select inner retinal neurons via multiple distinct cell death pathways. This severe phenotype is associated with disruptions to retinal central carbon metabolism, purine nucleotide synthesis, and amino acid pathways. Furthermore, transcriptomic and immunostaining approaches reveal dysregulation of a collection of photoreceptor and synapse-specific genes in NMNAT1 knockout retinas prior to detectable morphological or metabolic alterations. Collectively, our study reveals previously unrecognized complexity in NMNAT1-associated retinal degeneration and suggests a yet-undescribed role for NMNAT1 in gene regulation during photoreceptor terminal differentiation.

2013 ◽  
Vol 12 (6) ◽  
pp. 776-793 ◽  
Author(s):  
Xenie Johnson ◽  
Jean Alric

ABSTRACT The metabolism of microalgae is so flexible that it is not an easy task to give a comprehensive description of the interplay between the various metabolic pathways. There are, however, constraints that govern central carbon metabolism in Chlamydomonas reinhardtii that are revealed by the compartmentalization and regulation of the pathways and their relation to key cellular processes such as cell motility, division, carbon uptake and partitioning, external and internal rhythms, and nutrient stress. Both photosynthetic and mitochondrial electron transfer provide energy for metabolic processes and how energy transfer impacts metabolism and vice versa is a means of exploring the regulation and function of these pathways. A key example is the specific chloroplast localization of glycolysis/gluconeogenesis and how it impacts the redox poise and ATP budget of the plastid in the dark. To compare starch and lipids as carbon reserves, their value can be calculated in terms of NAD(P)H and ATP. As microalgae are now considered a potential renewable feedstock, we examine current work on the subject and also explore the possibility of rerouting metabolism toward lipid production.


2016 ◽  
Vol 24 (5) ◽  
pp. 728-739 ◽  
Author(s):  
Xiaojing Liu ◽  
Iris L. Romero ◽  
Lacey M. Litchfield ◽  
Ernst Lengyel ◽  
Jason W. Locasale

Author(s):  
Colin C. Anderson ◽  
John O. Marentette ◽  
Kendra M. Prutton ◽  
Abhishek K. Rauniyar ◽  
Julie A. Reisz ◽  
...  

The Analyst ◽  
2015 ◽  
Vol 140 (10) ◽  
pp. 3356-3361 ◽  
Author(s):  
Leyu Yan ◽  
Wenna Nie ◽  
Haitao Lv

The regulatory effects of the HPI virulence genes on central carbon metabolism differentiate UPEC from non-UPEC.


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