Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis.

Peroxiredoxin 6 (PRDX6) is a multifunctional enzyme involved in phospholipid peroxide repair and metabolism. In this study we investigated the global lipid composition of a human hepatocarcinoma cell line SNU475 lacking PRDX6 and lipid related cellular processes. There was a general decrease in multiple lipids species upon loss of PRDX6, in particular sphingomyelins and acylcarnitines, consistent with previously observed alterations in cell signaling pathways and mitochondrial dysfunction.

microRNA-1 Regulates Metabolic Flexibility in Skeletal Muscle via Pyruvate Metabolism.

MicroRNA-1 (miR-1) is the most abundant miRNA in adult skeletal muscle. To determine the function of miR-1 in adult skeletal muscle, we generated an inducible, skeletal muscle-specific miR-1 knockout (KO) mouse. Integration of RNA-sequencing (RNA-seq) data from miR-1 KO muscle with Argonaute 2 enhanced crosslinking and immunoprecipitation sequencing (AGO2 eCLIP-seq) from human skeletal muscle identified miR-1 target genes involved with glycolysis and pyruvate metabolism.

Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing.

Objectives: A decline in mitochondrial function and increased susceptibility to oxidative stress is a hallmark of ageing. Exercise endogenously generates reactive oxygen species (ROS) in skeletal muscle and promotes mitochondrial remodelling resulting in improved mitochondrial function. It is unclear how exercise induced redox signalling results in alterations in mitochondrial dynamics and morphology.

Redox regulation of UPR signalling and mitochondrial ER contact sites.

Mitochondria and the endoplasmic reticulum (ER) have a synergistic relationship and are key regulatory hubs in maintaining cell homeostasis. Communication between these organelles is mediated by mitochondria ER contact sites (MERCS), allowing the exchange of material and information, modulating calcium homeostasis, redox signalling, lipid transfer and the regulation of mitochondrial dynamics. MERCS are dynamic structures that allow cells to respond to changes in the intracellular environment under normal homeostatic conditions, while their assembly/disassembly are affected by pathophysiological conditions such as ageing and disease.

Quality assessment of LNP-RNA therapeutics with orthogonal analytical techniques.

The availability of analytical methods for the characterization of lipid nanoparticles (LNPs) for in-vivo intracellular delivery of nucleic acids is critical for the fast development of innovative RNA therapies. In this study, analytical protocols to measure (i) chemical composition, (ii) drug loading, (iii) particle size, concentration, and stability as well as (iv) structure and morphology were evaluated and compared based on a comprehensive characterization strategy linking key physical and chemical properties to in-vitro efficacy and toxicity. Furthermore, the measurement protocols were assessed either by testing the reproducibility and robustness of the same technique in different laboratories, or by a correlative approach, comparing measurement results of the same attribute with orthogonal techniques.