Human mitochondrial RNA decay mediated by PNPase–hSuv3 complex takes place in distinct foci

Borowski, Lukasz S.; Dziembowski, Andrzej; Hejnowicz, Monika S.; Stępień, Piotr P.; Szczęsny, Roman J.

doi:10.1093/nar/gks1130

Cited by 186 publications

(217 citation statements)

References 71 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…Here, we revealed that Dss1 interacts specifically with the large ribosomal subunit, whereas Suv3 is mainly a component of the nucleoid-MIOREX complex, in line with previous observations that it copurifies with mitochondrial ribosomes (Dziembowski et al, 2003) and a cluster-like organization adjacent to RNA and DNA (Borowski et al, 2013). The interaction of an RNase with the ribosome is reminiscent of the situation in bacteria, where RNase R binding to the small ribosomal subunit (Malecki et al, 2014) both stabilizes the enzyme and sequesters it from undesired spontaneous nucleolytic activity (Liang and Deutscher, 2013).…”

Section: Discussionsupporting

confidence: 92%

“…Several recent studies in mammalian cells have shown that RNA degradation and newly transcribed RNA are found in foci that are located in vicinity to the mitochondrial DNA (Antonicka et al, 2013;Borowski et al, 2013;Jourdain et al, 2013;Lee et al, 2013). These RNA granules also contain RNA-binding proteins, methyltransferases, and ribosomal proteins, therefore likely representing the nucleoid-MIOREX complexes identified here.…”

Section: Discussionmentioning

confidence: 54%

See 1 more Smart Citation

Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies

et al. 2015

View full text Add to dashboard Cite

Mitochondria contain their own genetic system that provides subunits of the complexes driving oxidative phosphorylation. A quarter of the mitochondrial proteome participates in gene expression, but how all these factors are orchestrated and spatially organized is currently unknown. Here, we established a method to purify and analyze native and intact complexes of mitochondrial ribosomes. Quantitative mass spectrometry revealed extensive interactions of ribosomes with factors involved in all the steps of posttranscriptional gene expression. These interactions result in large expressosome-like assemblies that we termed mitochondrial organization of gene expression (MIOREX) complexes. Superresolution microscopy revealed that most MIOREX complexes are evenly distributed throughout the mitochondrial network, whereas a subset is present as nucleoid-MIOREX complexes that unite the whole spectrum of organellar gene expression. Our work therefore provides a conceptual framework for the spatial organization of mitochondrial protein synthesis that likely developed to facilitate gene expression in the organelle.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 54%

Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies

et al. 2015

View full text Add to dashboard Cite

show abstract

“…At least three distinct types of foci relevant to mtDNA expression have been identified and visualized within the mitochondrial matrix of human cells. Those are the mitochondrial nucleoids, RNA granules and the RNA degradosome [156]. Here we will discuss the available data suggesting that the nucleoid and the RNA granule could be the factories where mitoribosomes are assembled.…”

Section: Nucleoids Rna Granules and Mitoribosome Assemblymentioning

confidence: 99%

Mitochondrial ribosome assembly in health and disease

et al. 2015

View full text Add to dashboard Cite

The ribosome is a structurally and functionally conserved macromolecular machine universally responsible for catalyzing protein synthesis. Within eukaryotic cells, mitochondria contain their own ribosomes (mitoribosomes), which synthesize a handful of proteins, all essential for the biogenesis of the oxidative phosphorylation system. High-resolution cryo-EM structures of the yeast, porcine and human mitoribosomal subunits and of the entire human mitoribosome have uncovered a wealth of new information to illustrate their evolutionary divergence from their bacterial ancestors and their adaptation to synthesis of highly hydrophobic membrane proteins. With such structural data becoming available, one of the most important remaining questions is that of the mitoribosome assembly pathway and factors involved. The regulation of mitoribosome biogenesis is paramount to mitochondrial respiration, and thus to cell viability, growth and differentiation. Moreover, mutations affecting the rRNA and protein components produce severe human mitochondrial disorders. Despite its biological and biomedical significance, knowledge on mitoribosome biogenesis and its deviations from the much-studied bacterial ribosome assembly processes is scarce, especially the order of rRNA processing and assembly events and the regulatory factors required to achieve fully functional particles. This article focuses on summarizing the current available information on mitoribosome assembly pathway, factors that form the mitoribosome assembly machinery, and the effect of defective mitoribosome assembly on human health.

show abstract

“…Western blotting was performed similar to the description by Ford et al (9), and all antibodies were purchased from Cell Signaling. ATP concentration was determined in freeze-clamped liver tissue according to the manufacturer's instruction (ab113849; Abcam) (30).…”

Section: Analytical Measurementsmentioning

confidence: 99%

Salsalate (Salicylate) Uncouples Mitochondria, Improves Glucose Homeostasis, and Reduces Liver Lipids Independent of AMPK-β1

et al. 2016

View full text Add to dashboard Cite

Salsalate is a prodrug of salicylate that lowers blood glucose in patients with type 2 diabetes (T2D) and reduces nonalcoholic fatty liver disease (NAFLD) in animal models; however, the mechanism mediating these effects is unclear. Salicylate directly activates AMPK via the β1 subunit, but whether salsalate requires AMPK-β1 to improve T2D and NAFLD has not been examined. Therefore, wild-type (WT) and AMPK-β1-knockout (AMPK-β1KO) mice were treated with a salsalate dose resulting in clinically relevant serum salicylate concentrations (~1 mmol/L). Salsalate treatment increased VO 2 , lowered fasting glucose, improved glucose tolerance, and led to an ~55% reduction in liver lipid content. These effects were observed in both WT and AMPK-β1KO mice. To explain these AMPK-independent effects, we found that salicylate increases oligomycin-insensitive respiration (state 4o) and directly increases mitochondrial proton Corresponding author: Gregory R. Steinberg, gsteinberg@mcmaster.ca. Duality of Interest. No potential conflicts of interest relevant to this article were reported.Author Contributions. B.K.S. and G.R.S. designed research studies, analyzed data, and wrote the manuscript. B.K.S., R.J.F., E.M.D., A.E.G., M.C.H., V.P.H., E.A.D., K.M., J.D.C., E.P.M., and C.G.R.P. conducted experiments and analyzed data. B.K.S., R.J.F., E.M.D., A.E.G., V.P.H., E.A.D., K.M., J.D.C., E.P.M., B.E.K., M.A.T., and G.R.S. edited the manuscript. G.R.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-0564/-/DC1. Diabetes. Author manuscript; available in PMC 2017 January 12.Published in final edited form as:Diabetes. 2016 November ; 65(11): 3352-3361. doi:10.2337/db16-0564. CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptconductance at clinical concentrations. This uncoupling effect is tightly correlated with the suppression of de novo lipogenesis. Salicylate is also able to stimulate brown adipose tissue respiration independent of uncoupling protein 1. These data indicate that the primary mechanism by which salsalate improves glucose homeostasis and NAFLD is via salicylate-driven mitochondrial uncoupling.Nonalcoholic fatty liver disease (NAFLD) is considered an important contributing factor to the development of insulin resistance and type 2 diabetes (T2D) (1). Despite the rising prevalence of NAFLD and importance for the development of T2D, there are currently no pharmacological approaches for the treatment of this disease (2).Salsalate is a prodrug of salicylate and is hydrolyzed in the small intestine to produce two molecules of salicylate (3,4). The circulating concentration of salicylate in humans administered salsalate in T2D clinical trials is ~1 mmol/L (5-8). Salsalate has also been shown to improve symptoms of NAFLD (9) and nonalcoholic steatohepatitis in...

show abstract

Human mitochondrial RNA decay mediated by PNPase–hSuv3 complex takes place in distinct foci

Cited by 186 publications

References 71 publications

Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies

Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies

Mitochondrial ribosome assembly in health and disease

Salsalate (Salicylate) Uncouples Mitochondria, Improves Glucose Homeostasis, and Reduces Liver Lipids Independent of AMPK-β1

Contact Info

Product

Resources

About