Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism
Joni Nikkanen,Saara Forsström,Liliya Euro,Ilse Paetau,Rebecca A. Kohnz,Liya Wang,Dmitri Chilov,Jenni Viinamäki,Anne Roivainen,Päivi Marjamäki,Heidi Liljenbäck,Sofia Ahola,Jana Buzkova,Mügen Terzioglu,Nahid Akhtar Khan,Sini Pirnes-Karhu,Anders Paetau,Tuula Lönnqvist,Antti Sajantila,Pirjo Isohanni,Henna Tyynismaa,Daniel K. Nomura,Brendan J. Battersby,Vidya Velagapudi,Christopher Carroll,Anu Suomalainen +25 more
TLDR
It is reported that mtDNA replication disorders caused by TWINKLE mutations-mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)-remodel cellular dNTP pools in mice are reported and targets for metabolic therapy are offered.About:
This article is published in Cell Metabolism.The article was published on 2016-04-12 and is currently open access. It has received 220 citations till now. The article focuses on the topics: Mitochondrial DNA replication & Transsulfuration.read more
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Journal ArticleDOI
One-Carbon Metabolism in Health and Disease
TL;DR: The fundamentals of mammalian 1C metabolism, including the pathways active in different compartments, cell types, and biological states, are reviewed and new opportunities for selective therapeutic intervention are highlighted.
Journal ArticleDOI
Serine and one-carbon metabolism in cancer.
Ming Yang,Karen H. Vousden +1 more
TL;DR: The non-essential amino acid serine supports several metabolic processes that are crucial for the growth and survival of proliferating cells, including protein, amino acid and glutathione synthesis, as an important one-carbon donor to the folate cycle.
Journal ArticleDOI
A sensitive assay for dNTPs based on long synthetic oligonucleotides, EvaGreen dye and inhibitor-resistant high-fidelity DNA polymerase.
TL;DR: A simple non-radioactive microplate assay for the quantification of dNTPs with a minimum requirement of 4–12 mg of biopsy material based on long synthetic single-stranded DNA templates, an inhibitor-resistant high-fidelity DNA polymerase, and the double-strander-DNA-binding EvaGreen dye that quantified reliably and discriminated well against ribonucleotides.
Journal ArticleDOI
Mitochondrial dysfunction remodels one-carbon metabolism in human cells
Xiaoyan Robert Bao,Xiaoyan Robert Bao,Xiaoyan Robert Bao,Shao En Ong,Olga Goldberger,Jun Peng,Jun Peng,Rohit Sharma,Dawn A. Thompson,Scott B. Vafai,Scott B. Vafai,Andrew G. Cox,Eizo Marutani,Fumito Ichinose,Wolfram Goessling,Wolfram Goessling,Aviv Regev,Aviv Regev,Steven A. Carr,Clary B. Clish,Vamsi K. Mootha,Vamsi K. Mootha,Vamsi K. Mootha +22 more
TL;DR: Two lines of evidence are provided that mitochondrial respiratory chain dysfunction leads to alterations in one-carbon metabolism pathways and that lesioning the respiratory chain impairs mitochondrial production of formate from serine, and that in some cells, respiratory chain inhibition leads to growth defects upon serine withdrawal that are rescuable with purine or formate supplementation.
Journal ArticleDOI
Mitochondrial diseases: the contribution of organelle stress responses to pathology
TL;DR: Insight is emerging from recent research that investigated defects in mitochondrial protein synthesis and mitochondrial DNA maintenance, which showed that many cell-specific stress responses are induced in response to mitochondrial dysfunction.
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