Emerging Lysosomal Functions for Photoreceptor Cell Homeostasis and Survival

Lysosomes are membrane-bound cell organelles that respond to nutrient changes and are implicated in cell homeostasis and clearance mechanisms, allowing effective adaptation to specific cellular needs. The relevance of the lysosome has been elucidated in a number of different contexts. Of these, the retina represents an interesting scenario to appreciate the various functions of this organelle in both physiological and pathological conditions. Growing evidence suggests a role for lysosome-related mechanisms in retinal degeneration. Abnormal lysosomal activation or inhibition has dramatic consequences on photoreceptor cell homeostasis and impacts extensive cellular function, which in turn affects vision. Based on these findings, a series of therapeutic methods targeting lysosomal processes could offer treatment for blindness conditions. Here, we review the recent findings on membrane trafficking, subcellular organization, mechanisms by which lysosome/autophagy pathway impairment affects photoreceptor cell homeostasis and the recent advances on developing efficient lysosomal-based therapies for retinal disorders.

North and East African mitochondrial genetic variation needs further characterization towards precision medicine

Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This requires a comprehensive catalogue of commonly observed genetic variations in the mitochondria for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied. Towards this, we have created the most comprehensive quality-controlled North and East African mitochondrial dataset to date by compiling 11 published cohorts with novel data of mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n=2,504) and the Human Genome Diversity Project (n=828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination. Using a subset of high-coverage mitochondrial sequences we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1. This demonstrates common hitherto unexplored variants in mitochondrial genomes of the North and East African region that lead to novel phylogenetic relationships, calling for further in-depth population genetic studies in that region.

Lighting up Individual Organelles With Fluorescent Carbon Dots

Cell organelles play crucial roles in the normal functioning of an organism, therefore the disruption of their operation is associated with diseases and in some cases death. Thus, the detection and monitoring of the activities within these organelles are of great importance. Several probes based on graphene oxide, small molecules, and other nanomaterials have been developed for targeting specific organelles. Among these materials, organelle-targeted fluorescent probes based on carbon dots have attracted substantial attention in recent years owing to their superior characteristics, which include facile synthesis, good photostability, low cytotoxicity, and high selectivity. The ability of these probes to target specific organelles enables researchers to obtain valuable information for understanding the processes involved in their functions and/or malfunctions and may also aid in effective targeted drug delivery. This review highlights recently reported organelle-specific fluorescent probes based on carbon dots. The precursors of these carbon dots are also discussed because studies have shown that many of the intrinsic properties of these probes originate from the precursor used. An overview of the functions of the discussed organelles, the types of probes used, and their advantages and limitations are also provided. Organelles such as the mitochondria, nucleus, lysosomes, and endoplasmic reticulum have been the central focus of research to date, whereas the Golgi body, centrosome, vesicles, and others have received comparatively little attention. It is therefore the hope of the authors that further studies will be conducted in an effort to design probes with the ability to localize within these less studied organelles so as to fully elucidate the mechanisms underlying their function.

Anti-Yeast Synergistic Effects and Mode of Action of Australian Native Plant Essential Oils

Yeasts are the most common group of microorganisms responsible for spoilage of soft drinks and fruit juices due to their ability to withstand juice acidity and pasteurization temperatures and resist the action of weak-acid preservatives. Food industries are interested in the application of natural antimicrobial compounds as an alternative solution to the spoilage problem. This study attempts to investigate the effectiveness of three Australian native plant essential oils (EOs) Tasmanian pepper leaf (TPL), lemon myrtle (LM) and anise myrtle (AM) against weak-acid resistant yeasts, to identify their major bioactive compounds and to elucidate their anti-yeast mode of action. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC) were assessed for EOs against weak-acid resistant yeasts (Candida albicans, Candida krusei, Dekkera anomala, Dekkera bruxellensis, Rhodotorula mucilaginosa, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Zygosaccharomyces bailii and Zygosaccharomyces rouxii) and bacteria (Staphylococcus aureus and Escherichia coli). The EOs showed anti-yeast and antibacterial activity at concentrations ranging from 0.03–0.07 mg/mL and 0.22–0.42 mg/mL for TPL and 0.07–0.31 mg/mL and 0.83–1.67 mg/mL for LM, respectively. The EOs main bioactive compounds were identified as polygodial in TPL, citral (neral and geranial) in LM and anethole in AM. No changes in the MICs of the EOs were observed in the sorbitol osmotic protection assay but were found to be increased in the ergosterol binding assay after the addition of exogenous ergosterol. Damaging of the yeast cell membrane, channel formation, cell organelles and ion leakage could be identified as the mode of action of TPL and LM EOs. The studied Australian native plant EOs showed potential as natural antimicrobials that could be used in the beverage and food industry against the spoilage causing yeasts.

Efficient recurrent neural network methods for anomalously diffusing single particle short and noisy trajectories

Anomalous diffusion occurs at very different scales in nature, from atomic systems to motions in cell organelles, biological tissues or ecology, and also in artificial materials, such as cement. Being able to accurately measure the anomalous exponent associated to a given particle trajectory, thus determining whether the particle subdiffuses, superdiffuses or performs normal diffusion, is of key importance to understand the diffusion process. Also it is often important to trustingly identify the model behind the trajectory, as it this gives a large amount of information on the system dynamics. Both aspects are particularly difficult when the input data are short and noisy trajectories. It is even more difficult if one cannot guarantee that the trajectories output in experiments are homogeneous, hindering the statistical methods based on ensembles of trajectories. We present a data-driven method able to infer the anomalous exponent and to identify the type of anomalous diffusion process behind single, noisy and short trajectories, with good accuracy. This model was used in our participation in the Anomalous Diffusion (AnDi) Challenge. A combination of convolutional and recurrent neural networks was used to achieve state-of-the-art results when compared to methods participating in the AnDi Challenge, ranking top 4 in both classification and diffusion exponent regression.

The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes

Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.

Dynamic Cell Imaging: application to the diatom Phaeodactylum tricornutum under environmental stresses

The dynamic movement of cell organelles is an important and poorly understood component of cellular organisation and metabolism. In this work we present a non-invasive non-destructive method (Dynamic Cell Imaging, DCI) based on light scattering and interferometry to monitor dynamic events within photosynthetic cells using the diatom Phaeodactylum tricornutum as a model system. For this monitoring we acquire few seconds movies of the signals that are related to the motion of dynamic structures within the cell (denoted scatterers), followed by a statistical analysis of each pixel time series. Illuminating P.tricornutum with LEDs of different wavelengths associated to short pulsed or continuous-wave modes of illumination revealed that dynamic movements depend on chloroplast activity, in agreement with the reduction in the number of pixels with dynamic behaviour after addition of photosystemII inhibitors. We studied P. tricornutum under two environmentally relevant stresses, iron and phosphate deficiency. The major dynamic sites were located within lipid droplets and chloroplast envelope membranes. By comparing standard deviation and cumulative sum analysis of the time series, we showed that within the droplets two types of scatterer movement could be observed: random motions (Brownian type) but also anomalous movements corresponding to a drift which may relate to molecular fluxes within a cell. The method appears valuable for studying the effects of various environments on a large variety of microalgae in the laboratory as well as in natural aquatic environments.

Arabidopsis thaliana myosin XIK is recruited to the Golgi through interaction with a MyoB receptor

Plant cell organelles are highly mobile and their positioning play key roles in plant growth, development and responses to changing environmental conditions. Movement is acto-myosin dependent. Despite controlling the dynamics of several organelles, myosin and myosin receptors identified so far in Arabidopsis thaliana generally do not localise to the organelles whose movement they control, raising the issue of how specificity is determined. Here we show that a MyoB myosin receptor, MRF7, specifically localises to the Golgi membrane and affects its movement. Myosin XI-K was identified as a putative MRF7 interactor through mass spectrometry analysis. Co-expression of MRF7 and XI-K tail triggers the relocation of XI-K to the Golgi, linking a MyoB/myosin complex to a specific organelle in Arabidopsis. FRET-FLIM confirmed the in vivo interaction between MRF7 and XI-K tail on the Golgi and in the cytosol, suggesting that myosin/myosin receptor complexes perhaps cycle on and off organelle membranes. This work supports a traditional mechanism for organelle movement where myosins bind to receptors and adaptors on the organelle membranes, allowing them to actively move on the actin cytoskeleton, rather than passively in the recently proposed cytoplasmic streaming model.