A Compendium of Information on the Lysosome

Bouhamdani, Nadia; Comeau, Dominique; Turcotte, Sandra

doi:10.3389/fcell.2021.798262

Cited by 31 publications

(17 citation statements)

References 279 publications

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“…Similarly to naked ASOs, the SEM micrographs (Figure S5) reveal that 34 S 15 -ASO enrichments overlap with electron dense structures identified as lysosomes, correlating with previous studies . Note that not all of the lysosomes visible on the BSE images present 34 S 15 -ASO enrichments, as lysosomes are a heterogeneous assortment of organelles, in terms of morphology and function, encompassing endolysosomes, phagolysosomes, and autolysosomes. , …”

Section: Resultssupporting

confidence: 86%

Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS

Becquart

Stulz

Thomen³

et al. 2022

Anal. Chem.

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Antisense oligonucleotide (ASO)-based therapeutics hold great potential for the treatment of a variety of diseases. Therefore, a better understanding of cellular delivery, uptake, and trafficking mechanisms of ASOs is highly important for early-stage drug discovery. In particular, understanding the biodistribution and quantifying the abundance of ASOs at the subcellular level are needed to fully characterize their activity. Here, we used a combination of electron microscopy and NanoSIMS to assess the subcellular concentrations of a 34 S-labeled GalNAc-ASO and a naked ASO in the organelles of primary human hepatocytes. We first cross-validated the method by including a 127 I-labeled ASO, finding that the absolute concentration of the lysosomal ASO using two independent labeling strategies gave matching results, demonstrating the strength of our approach. This work also describes the preparation of external standards for absolute quantification by NanoSIMS. For both the 34 S and 127 I approaches used for our quantification methodology, we established the limit of detection (5 and 2 μM, respectively) and the lower limit of quantification (14 and 5 μM, respectively).

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Section: Resultssupporting

confidence: 86%

Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS

Becquart

Stulz

Thomen³

et al. 2022

Anal. Chem.

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“…Recent advances in lysosome biology have been comprehensively described in excellent recent reviews. 18,19 Here, we focus on how lysosomes are recognized before describing state-of-the-art methods to analyze lysosome morphology, positioning, motility and function.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

Current methods to analyze lysosome morphology, positioning, motility and function

Barral

Staiano

Almeida

et al. 2022

Traffic

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Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground‐breaking discoveries on an organelle that continues to surprise and excite cell biologists.

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“…Lysosomes are membrane-enclosed organelles that contain an array of enzymes capable of breaking down non-functional cell organelles and biomolecules. In addition to this function, lysomomes are essential for nutrient sensing and metabolic adaptation [ 244 ]. FFA accumulation, seen in NAFLD, evokes pore formation in lysosome membranes, releasing ROS and other apoptosis-inducing factors [ 245 ].…”

Section: Oxidative Stress In Nafldmentioning

confidence: 99%

NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook

Nascè¹,

Gariani

Jornayvaz

et al. 2022

Antioxidants

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Nonalcoholic fatty liver disease (NAFLD), characterized by ectopic fat accumulation in hepatocytes, is closely linked to insulin resistance and is the most frequent complication of type 2 diabetes mellitus (T2DM). One of the features connecting NAFLD, insulin resistance and T2DM is cellular oxidative stress. Oxidative stress refers to a redox imbalance due to an inequity between the capacity of production and the elimination of reactive oxygen species (ROS). One of the major cellular ROS sources is NADPH oxidase enzymes (NOX-es). In physiological conditions, NOX-es produce ROS purposefully in a timely and spatially regulated manner and are crucial regulators of various cellular events linked to metabolism, receptor signal transmission, proliferation and apoptosis. In contrast, dysregulated NOX-derived ROS production is related to the onset of diverse pathologies. This review provides a synopsis of current knowledge concerning NOX enzymes as connective elements between NAFLD, insulin resistance and T2DM and weighs their potential relevance as pharmacological targets to alleviate fatty liver disease.

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A Compendium of Information on the Lysosome

Cited by 31 publications

References 279 publications

Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS

Intracellular Absolute Quantification of Oligonucleotide Therapeutics by NanoSIMS

Current methods to analyze lysosome morphology, positioning, motility and function

NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook

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