👤 Matthew Lorincz

Coenzyme Q10 (CoQ10) plays a crucial role in facilitating electron transport during oxidative phosphorylation, thus contributing to cellular energy production. Statin treatment causes a decrease in CoQ10 levels in muscle tissue as well as in serum, which may contribute to the musculoskeletal side effects. Therefore, we aimed to assess the effect of newly initiated statin treatment on serum CoQ10 levels after acute ST-elevation myocardial infarction (STEMI) and the correlation of CoQ10 levels with key biomarkers of subclinical or clinically overt myopathy. In this study, we enrolled 67 non-diabetic, statin-naïve early-onset STEMI patients with preserved renal function. Plasma CoQ10 level was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC/MS-MS), while the myopathy marker serum fatty acid-binding protein 3 (FABP3) level was measured with enzyme-linked immunosorbent assay (ELISA) at hospital admission and after 3 months of statin treatment. The treatment significantly decreased the plasma CoQ10 (by 43%) and FABP3 levels (by 79%) as well as total cholesterol, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B100 (ApoB100), and oxidized LDL (oxLDL) levels. The change in CoQ10 level showed significant positive correlations with the changes in total cholesterol, LDL-C, ApoB100, and oxLDL levels, while it did not correlate with the change in FABP3 level. Our results prove the CoQ10-reducing effect of statin treatment and demonstrate its lipid-lowering efficacy but contradict the role of CoQ10 reduction in statin-induced myopathy. Show less

Histone H3 trimethylation of lysine 9 (H3K9me3) and proteins of the heterochromatin protein 1 (HP1) family are hallmarks of heterochromatin, a state of compacted DNA essential for genome stability and long-term transcriptional silencing. The mechanisms by which H3K9me3 and HP1 contribute to chromatin condensation have been speculative and controversial. Here we demonstrate that human HP1β is a prototypic HP1 protein exemplifying most basal chromatin binding and effects. These are caused by dimeric and dynamic interaction with highly enriched H3K9me3 and are modulated by various electrostatic interfaces. HP1β bridges condensed chromatin, which we postulate stabilizes the compacted state. In agreement, HP1β genome-wide localization follows H3K9me3-enrichment and artificial bridging of chromatin fibres is sufficient for maintaining cellular heterochromatic conformation. Overall, our findings define a fundamental mechanism for chromatin higher order structural changes caused by HP1 proteins, which might contribute to the plastic nature of condensed chromatin. Show less