bims-cytox1 2017-05-21 papers

Issue of 2017‒05‒21
two papers selected by
Gavin McStay
New York Institute of Technology

Mitochondrion. 2017 May 09. pii: S1567-7249(17)30129-0. [Epub ahead of print]

Identification of FASTKD2 compound heterozygous mutations as the underlying cause of autosomal recessive MELAS-like syndrome.

Da Hye Yoo, Young-Chul Choi, Da Eun Nam, Sun Seong Choi, Jiwon Kim, Byung-Ok Choi, Ki Wha Chung.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many parts of the body, particularly the brain and muscles. This study examined a Korean MELAS-like syndrome patient with seizure, stroke-like episode, and optic atrophy. Target sequencing of whole mtDNA and 73 nuclear genes identified compound heterozygous mutations p.R205X and p.L255P in the FASTKD2. Each of his unaffected parents has one of the two mutations, and both mutations were not found in 302 controls. FASTKD2 encodes a FAS-activated serine-threonine (FAST) kinase domain 2 which locates in the mitochondrial inner compartment. A FASTKD2 nonsense mutation was once reported as the cause of a recessive infantile mitochondrial encephalomyopathy. The present case showed relatively mild symptoms with a late onset age, compared to a previous patient with FASTKD2 mutation, implicating an inter-allelic clinical heterogeneity. Because this study is the second report of an autosomal recessive mitochondrial encephalomyopathy patient with a FASTKD2 mutation, it will extend the phenotypic spectrum of the FASTKD2 mutation.

Keywords: FASTKD2; Korean; MELAS; Mitochondrial encephalomyopathy; Target sequencing

DOI: https://doi.org/10.1016/j.mito.2017.05.005

G3 (Bethesda). 2017 May 12. pii: g3.117.042655. [Epub ahead of print]

Manipulating the Mitochondrial Genome To Enhance Cattle Embryo Development.

Kanokwan Srirattana, Justin C St John.

The mixing of mitochondrial DNA (mtDNA) from the donor cell and the recipient oocyte in embryos and offspring derived from somatic cell nuclear transfer (SCNT) compromises genetic integrity and affects embryo development. We set out to generate SCNT embryos that inherited their mtDNA from the recipient oocyte only, as is the case following natural conception. Whilst SCNT blastocysts produced from Holstein (Bos Taurus) fibroblasts depleted of their mtDNA and oocytes derived from Angus (Bos Taurus) cattle possessed oocyte mtDNA only, the co-existence of donor cell and oocyte mtDNA resulted in blastocysts derived from non-depleted cells. Moreover, the use of the reprogramming agent, Trichostatin A (TSA), further improved the development of embryos derived from depleted cells. RNA-seq analysis highlighted 35 differentially expressed genes from the comparison between blastocysts generated from non-depleted cells and blastocysts from depleted cells, both in the presence of TSA. The only differences between these two sets of embryos were the presence of donor cell mtDNA and a significantly higher mtDNA copy number for embryos derived from non-depleted cells. Furthermore, the use of TSA on embryos derived from depleted cells positively modulated the expression of CLDN8, TMEM38A and FREM1, which affect embryonic development. In conclusion, SCNT embryos produced by mtDNA depleted donor cells have the same potential to develop to the blastocyst stage without the presumed damaging effect resulting from the mixture of donor and recipient mtDNA.

Keywords: cattle; depletion; embryo development; mitochondrial DNA; somatic cell nuclear transfer

DOI: https://doi.org/10.1534/g3.117.042655