bims-cytox1 2017-12-24 papers

Issue of 2017‒12‒24
two papers selected by
Gavin McStay
New York Institute of Technology

Cell Syst. 2017 Dec 12. pii: S2405-4712(17)30540-9. [Epub ahead of print]

Multi-omics Reveal Specific Targets of the RNA-Binding Protein Puf3p and Its Orchestration of Mitochondrial Biogenesis.

Christopher P Lapointe, Jonathan A Stefely, Adam Jochem, Paul D Hutchins, Gary M Wilson, Nicholas W Kwiecien, Joshua J Coon, Marvin Wickens, David J Pagliarini.

Coenzyme Q (CoQ) is a redox-active lipid required for mitochondrial oxidative phosphorylation (OxPhos). How CoQ biosynthesis is coordinated with the biogenesis of OxPhos protein complexes is unclear. Here, we show that the Saccharomyces cerevisiae RNA-binding protein (RBP) Puf3p regulates CoQ biosynthesis. To establish the mechanism for this regulation, we employed a multi-omic strategy to identify mRNAs that not only bind Puf3p but also are regulated by Puf3p in vivo. The CoQ biosynthesis enzyme Coq5p is a critical Puf3p target: Puf3p regulates the abundance of Coq5p and prevents its detrimental hyperaccumulation, thereby enabling efficient CoQ production. More broadly, Puf3p represses a specific set of proteins involved in mitochondrial protein import, translation, and OxPhos complex assembly (pathways essential to prime mitochondrial biogenesis). Our data reveal a mechanism for post-transcriptionally coordinating CoQ production with OxPhos biogenesis, and they demonstrate the power of multi-omics for defining genuine targets of RBPs.

Keywords: COQ5; PUF3; RNA binding protein; biogenesis; coenzyme Q; complex Q; mitochondria; multi-omic; transomic; ubiquinone

DOI: https://doi.org/10.1016/j.cels.2017.11.012

JIMD Rep. 2017 Dec 17.

Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis.

C Bursle, K Riney, J Stringer, D Moore, G Gole, L S Kearns, D A Mackey, D Coman.

Leber Hereditary Optic Neuropathy is an inherited optic neuropathy caused by mitochondrial DNA point mutations leading to sudden, painless loss of vision. We report a case of an 8-year-old boy presenting with a radiological phenotype of longitudinally extensive transverse myelitis on a background of severe visual impairment secondary to Leber Hereditary Optic Neuropathy (LHON). He was found to have dual mitochondrial DNA mutations at 14484 (MTND6 gene) and 4160 (MTND1 gene) in a family with a severe form of LHON characterised by not only an unusually high penetrance of optic neuropathy, but also severe extra-ocular neurological complications. The m.14484T>C mutation is a common LHON mutation, but the m.4160T>C mutation is to our knowledge not reported outside this family and appears to drive the neurological manifestations. To our knowledge there have been no previous reports of spinal cord lesions in children with LHON.

Keywords: LHON plus; Leber Hereditary Optic Neuropathy; Longitudinally extensive transverse myelitis; Mitochondrial; Myelopathy; Transverse myelitis

DOI: https://doi.org/10.1007/8904_2017_79