Methyltransferases

Publication Title: 
Biochimica Et Biophysica Acta

This review describes our current understanding of the "traffic lights" that regulate sulfur flow through the methionine bionetwork in liver, which supplies two major homeostatic systems governing cellular methylation and antioxidant potential. Theoretical concepts derived from mathematical modeling of this metabolic nexus provide insights into the properties of this system, some of which seem to be paradoxical at first glance. Cellular needs supported by this network are met by use of parallel metabolic tracks that are differentially controlled by intermediates in the pathway.

Author(s): 
Martinov, M. V.
Vitvitsky, V. M.
Banerjee, R.
Ataullakhanov, F. I.
Publication Title: 
Cellular and molecular life sciences: CMLS

Metabolic homeostasis and interventions that influence nutrient uptake are well-established means to influence lifespan even in higher eukaryotes. Until recently, the molecular mechanisms explaining such an effect remained scantily understood. Sirtuins are a group of protein deacetylases that depend on the metabolic intermediate NAD(+) as a cofactor for their function. For this reason they sense metabolic stress and in turn function at multiple levels to exert proper metabolic adaptation.

Author(s): 
Cosentino, Claudia
Mostoslavsky, Raul
Publication Title: 
Nature Communications

A de novo G608G mutation in LMNA gene leads to Hutchinson-Gilford progeria syndrome. Mice lacking the prelamin A-processing metalloprotease, Zmpste24, recapitulate many of the progeroid features of Hutchinson-Gilford progeria syndrome. Here we show that A-type lamins interact with SUV39H1, and prelamin A/progerin exhibits enhanced binding capacity to SUV39H1, protecting it from proteasomal degradation and, consequently, increasing H3K9me3 levels. Depletion of Suv39h1 reduces H3K9me3 levels, restores DNA repair capacity and delays senescence in progeroid cells.

Author(s): 
Liu, Baohua
Wang, Zimei
Zhang, Le
Ghosh, Shrestha
Zheng, Huiling
Zhou, Zhongjun
Publication Title: 
Epigenetics

The role of methylation in the history of psychiatry has traversed a storied path. The original trans-methylation hypothesis was proposed at a time when chlorpromazine had been synthesized but not yet marketed as an antipsychotic (Thorazine). The premise was that abnormal metabolism led to the methylation of biogenic amines in the brains of schizophrenia patients and that these hallucinogenic compounds produced positive symptoms of the disease. At the time, some psychiatrists were interested in drugs such as mescaline and lysergic acid diethylamide that replicated clinical symptoms.

Author(s): 
Grayson, Dennis R.
Chen, Ying
Dong, Erbo
Kundakovic, Marija
Guidotti, Alessandro
Publication Title: 
PloS One

Withania somnifera is one of the most valuable medicinal plants used in Ayurvedic and other indigenous medicine systems due to bioactive molecules known as withanolides. As genomic information regarding this plant is very limited, little information is available about biosynthesis of withanolides. To facilitate the basic understanding about the withanolide biosynthesis pathways, we performed transcriptome sequencing for Withania leaf (101L) and root (101R) which specifically synthesize withaferin A and withanolide A, respectively.

Author(s): 
Gupta, Parul
Goel, Ridhi
Pathak, Sumya
Srivastava, Apeksha
Singh, Surya Pratap
Sangwan, Rajender Singh
Asif, Mehar Hasan
Trivedi, Prabodh Kumar
Publication Title: 
PloS One

Withania somnifera is one of the most valuable medicinal plants used in Ayurvedic and other indigenous medicine systems due to bioactive molecules known as withanolides. As genomic information regarding this plant is very limited, little information is available about biosynthesis of withanolides. To facilitate the basic understanding about the withanolide biosynthesis pathways, we performed transcriptome sequencing for Withania leaf (101L) and root (101R) which specifically synthesize withaferin A and withanolide A, respectively.

Author(s): 
Gupta, Parul
Goel, Ridhi
Pathak, Sumya
Srivastava, Apeksha
Singh, Surya Pratap
Sangwan, Rajender Singh
Asif, Mehar Hasan
Trivedi, Prabodh Kumar
Publication Title: 
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience

Alzheimer's disease (AD) neuropathology is characterized by the accumulation of phosphorylated tau and amyloid-beta peptides derived from the amyloid precursor protein (APP). Elevated blood levels of homocysteine are a significant risk factor for many age-related diseases, including AD. Impaired homocysteine metabolism favors the formation of S-adenosylhomocysteine, leading to inhibition of methyltransferase-dependent reactions.

Author(s): 
Sontag, Estelle
Nunbhakdi-Craig, Viyada
Sontag, Jean-Marie
Diaz-Arrastia, Ramon
Ogris, Egon
Dayal, Sanjana
Lentz, Steven R.
Arning, Erland
Bottiglieri, Teodoro
Publication Title: 
Gut Microbes

Although commensal microbes have been shown to modulate host immune responses, many of the bacterial factors that mediate immune regulation remain unidentified. Select strains of human-derived Lactobacillus reuteri synthesize immunomodulins that potently inhibit production of the inflammatory cytokine TNF. In this study, genetic and genomic approaches were used to identify and investigate L. reuteri genes required or human TNF immunomodulatory activity. Analysis of membrane fatty acids from multiple L.

Author(s): 
Jones, Sara E.
Whitehead, Kristi
Saulnier, Delphine
Thomas, Carissa M.
Versalovic, James
Britton, Robert A.
Publication Title: 
Autophagy

While autophagy is believed to be beneficial for life-span extension, it is controversial which forms or aspects of autophagy are responsible for this effect. We addressed this topic by analyzing the life span of yeast autophagy mutants under caloric restriction, a longevity manipulation. Surprisingly, we discovered that the majority of proteins involved in macroautophagy and several forms of microautophagy were dispensable for life-span extension.

Author(s): 
Tang, Fusheng
Watkins, Joseph W.
Bermudez, Maria
Gray, Russell
Gaban, Adam
Portie, Ken
Grace, Stephen
Kleve, Maurice
Craciun, Gheorghe
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