bims-cytox1 2017-06-11 papers

Issue of 2017‒06‒11
three papers selected by
Gavin McStay
New York Institute of Technology

J Mol Biol. 2017 Jul 07. pii: S0022-2836(17)30263-2. [Epub ahead of print]429(14): 2148-2160

Connection of Protein Transport and Organelle Contact Sites in Mitochondria.

Lars Ellenrieder, Heike Rampelt, Thomas Becker.

Mitochondrial biogenesis and function depend on the intensive exchange of molecules with other cellular compartments. The mitochondrial outer membrane plays a central role in this communication process. It is equipped with a number of specific protein machineries that enable the transport of proteins and metabolites. Furthermore, the outer membrane forms molecular contact sites with other cell organelles like the endoplasmic reticulum (ER), thus integrating mitochondrial function in cellular physiology. The best-studied mitochondrial organelle contact site, the ER-mitochondria encounter structure (ERMES) has been linked to many vital processes including mitochondrial division, inheritance, mitophagy, and phospholipid transport. Strikingly, ER-mitochondria contact sites are closely connected to outer membrane protein translocases. The translocase of the outer mitochondrial membrane (TOM) represents the general mitochondrial entry gate for precursor proteins that are synthesized on cytosolic ribosomes. The outer membrane also harbors the sorting and assembly machinery (SAM) that mediates membrane insertion of β-barrel proteins. Both of these essential protein translocases are functionally linked to ER-mitochondria contact sites. First, the SAM complex associates with an ERMES core component to promote assembly of the TOM complex. Second, several TOM components have been co-opted as ER-mitochondria tethers. We propose that protein import and organelle contact sites are linked to coordinate processes important for mitochondrial biogenesis.

Keywords: ERMES; SAM complex; TOM complex; mitochondria; organelle contact sites

DOI: https://doi.org/10.1016/j.jmb.2017.05.023

Development. 2017 Jul 01. 144(13): 2490-2503

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality.

Chunyang Zhang, Kristi L Montooth, Brian R Calvi.

Mitochondrial dysfunction can cause female infertility. An important unresolved issue is the extent to which incompatibility between mitochondrial and nuclear genomes contributes to female infertility. It has previously been shown that a mitochondrial haplotype from D. simulans (simw501 ) is incompatible with a nuclear genome from the D. melanogaster strain Oregon-R (OreR), resulting in impaired development, which was enhanced at higher temperature. This mito-nuclear incompatibility is between alleles of the nuclear-encoded mitochondrial tyrosyl-tRNA synthetase (Aatm) and the mitochondrial-encoded tyrosyl-tRNA that it aminoacylates. Here, we show that this mito-nuclear incompatibility causes a severe temperature-sensitive female infertility. The OreR nuclear genome contributed to death of ovarian germline stem cells and reduced egg production, which was further enhanced by the incompatibility with simw501 mitochondria. Mito-nuclear incompatibility also resulted in aberrant egg morphology and a maternal-effect on embryonic chromosome segregation and survival, which was completely dependent on the temperature and mito-nuclear genotype of the mother. Our findings show that maternal mito-nuclear incompatibility during Drosophila oogenesis has severe consequences for egg production and embryonic survival, with important broader relevance to human female infertility and mitochondrial replacement therapy.

Keywords: Drosophila; Embryogenesis; Mitochondria; Mitochondrial-nuclear incompatibility; Oogenesis; Stem cell

DOI: https://doi.org/10.1242/dev.151951

Oncotarget. 2017 May 15.

Down-regulation of MRPS23 inhibits rat breast cancer proliferation and metastasis.

Yan Gao, Fuyan Li, Hong Zhou, Yi Yang, Ruimin Wu, Yijia Chen, Wei Li, Yang Li, Xueqin Xu, Changbin Ke, Zhijun Pei.

Mitochondrial ribosomal protein S23 (MRPS23) has been shown to be involved in breast cancer cell proliferation and metastatic phenotypes of cervical cancer. Here we investigated its biological features in breast cancer for the first time. It demonstrated that knockdown of MRPS23 reduced breast cancer cell proliferation and induced apoptosis in vitro. Besides, shRNA targeting MRPS23 (shMRPS23) inhibited tumour proliferation and metastasis by blocking tumor angiogenesis in breast cancer xenograft rat model. Small animal positron emission tomography/computed tomography (PET/CT) with 2'-deoxy-2'-[18F] fluoro-D-glucose (FDG) was performed at four weeks after tumour cell injection. We found that FDG maximum standardized uptake value (SUVmax) significantly decreased by 31 ± 3% in the shMRPS23-treated group. But this change was not independent of metabolic tumour size. In addition, we also found that shMRPS23 could significantly suppress breast cancer metastasis through inhibiting epithelial mesenchymal transition (EMT) phenotype. The epithelial marker E-cadherin was increased, whereas the metastasis associated gene vimentin was decreased. Mechanistically, shMRPS23-treated tumours failed to progress through p53 and p21WAF1/CIP1 activation, but not cytochrome c-mediated pathway. These findings suggest that MRPS23 is a potential therapeutic target for interference of breast cancer proliferation, angiogenesis and metastasis.

Keywords: MRPS23; breast cancer; metastasis; p21 WAF1/CIP1; p53

DOI: https://doi.org/10.18632/oncotarget.17888