bims-tricox 2022-11-20 papers

Issue of 2022‒11‒20
two papers selected by
Yash Verma
University of Delhi South Campus

Naunyn Schmiedebergs Arch Pharmacol. 2022 Nov 17.

Inhibition of mitochondrial respiration by general anesthetic drugs.

Anton Fedorov, Alina Lehto, Jochen Klein.

General anesthetic drugs have been associated with various unwanted effects including an interference with mitochondrial function. We had previously observed increases of lactate formation in the mouse brain during anesthesia with volatile anesthetic agents. In the present work, we used mitochondria that were freshly isolated from mouse brain to test mitochondrial respiration and ATP synthesis in the presence of six common anesthetic drugs. The volatile anesthetics isoflurane, halothane, and (to a lesser extent) sevoflurane caused an inhibition of complex I of the electron transport chain in a dose-dependent manner. Significant effects were seen at concentrations that are reached under clinical conditions (< 0.5 mM). Pentobarbital and propofol also inhibited complex I but at concentrations that were two-fold higher than clinical EC50 values. Only propofol caused an inhibition of complex II. Complex IV respiration was not affected by either agent. Ketamine did not affect mitochondrial respiration. Similarly, all anesthetic agents except ketamine suppressed ATP production at high concentrations. Only halothane increased cytochrome c release indicating damage of the mitochondrial membrane. In summary, volatile general anesthetic agents as well as pentobarbital and propofol dose-dependently inhibit mitochondrial respiration. This action may contribute to depressive actions of the drugs in the brain.

Keywords: Halothane; Isoflurane; Ketamine; Pentobarbital; Propofol; Sevoflurane

DOI: https://doi.org/10.1007/s00210-022-02338-9

J Cell Sci. 2022 Nov 14. pii: jcs.260388. [Epub ahead of print]

An RNA granule for translation quality control in Saccharomyces cerevisiae.

James S Dhaliwal, Cristina Panozzo, Lionel Benard, William Zerges.

Cytoplasmic RNA granules compartmentalize phases of the translation cycle in eukaryotes. We previously reported the localization of oxidized RNA to cytoplasmic foci called oxidized RNA bodies (ORBs) in human cells. We show here that ORBs are RNA granules in Saccharomyces cerevisiae. Several lines of evidence support a role of ORBs in the compartmentalization of no-go decay and ribosome quality control, the translation quality control pathways that recognize and clear aberrant mRNAs, including those with oxidized bases. Translation is required by these pathways and ORBs. Translation quality control factors localize to ORBs. A substrate of translation quality control, a stalled mRNA-ribosome-nascent chain complex, localizes to ORBS. Translation quality control mutants have altered ORB numbers, sizes, or both. In addition, we identify 68 ORB proteins, by immunofluorescence staining directed by proteomics, which further support their role in translation quality control and reveal candidate new factors for these pathways.

Keywords: No-go decay; Oxidized RNA; RNA granules; Ribosome-associated quality control; Translation

DOI: https://doi.org/10.1242/jcs.260388