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      Disrupted brain mitochondrial morphology after in vivo hydrogen sulfide exposure

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          Abstract

          Changes in mitochondrial dynamics are often associated with dietary patterns, medical treatments, xenobiotics, and diseases. Toxic exposures to hydrogen sulfide (H 2S) harm mitochondria by inhibiting Complex IV and via other mechanisms. However, changes in mitochondrial dynamics, including morphology following acute exposure to H 2S, are not yet fully understood. This study followed mitochondrial morphology changes over time after a single acute LCt 50 dose of H 2S by examining electron microscopy thalami images of surviving mice. Our findings revealed that within the initial 48 h after H 2S exposure, mitochondrial morphology was impaired by H 2S, supported by the disruption and scarcity of the cristae, which are required to enhance the surface area for ATP production. At the 72-h mark point, a spectrum of morphological cellular changes was observed, and the disordered mitochondrial network, accompanied by the probable disruption of mitophagy, was tied to changes in mitochondrial shape. In summary, this study sheds light on how acute exposure to high levels of H 2S triggers alterations in mitochondrial shape and structure as early as 24 h that become more evident at 72 h post-exposure. These findings underscore the impact of H 2S on mitochondrial function and overall cellular health.

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          The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

          Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the “ARRIVE Essential 10,” which constitutes the minimum requirement, and the “Recommended Set,” which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
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            Mitochondrial dynamics: overview of molecular mechanisms

            Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as ‘mitochondrial dynamics’, in order to maintain their shape, distribution and size. Their transient and rapid morphological adaptations are crucial for many cellular processes such as cell cycle, immunity, apoptosis and mitochondrial quality control. Mutations in the core machinery components and defects in mitochondrial dynamics have been associated with numerous human diseases. These dynamic transitions are mainly ensured by large GTPases belonging to the Dynamin family. Mitochondrial fission is a multi-step process allowing the division of one mitochondrion in two daughter mitochondria. It is regulated by the recruitment of the GTPase Dynamin-related protein 1 (Drp1) by adaptors at actin- and endoplasmic reticulum-mediated mitochondrial constriction sites. Drp1 oligomerization followed by mitochondrial constriction leads to the recruitment of Dynamin 2 to terminate membrane scission. Inner mitochondrial membrane constriction has been proposed to be an independent process regulated by calcium influx. Mitochondrial fusion is driven by a two-step process with the outer mitochondrial membrane fusion mediated by mitofusins 1 and 2 followed by inner membrane fusion, mediated by optic atrophy 1. In addition to the role of membrane lipid composition, several members of the machinery can undergo post-translational modifications modulating these processes. Understanding the molecular mechanisms controlling mitochondrial dynamics is crucial to decipher how mitochondrial shape meets the function and to increase the knowledge on the molecular basis of diseases associated with morphology defects. This article will describe an overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals.
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              During autophagy mitochondria elongate, are spared from degradation and sustain cell viability

              Summary A plethora of cellular processes, including apoptosis, depend on regulated changes in mitochondrial shape and ultrastructure. Scarce is our understanding of the role of mitochondria and of their morphology during autophagy, a bulk degradation and recycling process of eukaryotic cells’ constituents. Here we show that mitochondrial morphology determines the cellular response to macroautophagy. When autophagy is triggered, mitochondria elongate in vitro and in vivo. Upon starvation cellular cAMP levels increase and protein kinase A (PKA) becomes activated. PKA in turn phosphorylates the pro-fission dynamin related protein 1 (DRP1) that is therefore retained in the cytoplasm, leading to unopposed mitochondrial fusion. Elongated mitochondria are spared from autophagic degradation, possess more cristae, increase dimerization and activity of ATP synthase, and maintain ATP production. When elongation is genetically or pharmacologically blocked, mitochondria conversely consume ATP, precipitating starvation-induced death. Thus, regulated changes in mitochondrial morphology determine the fate of the cell during autophagy.
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                Author and article information

                Contributors
                wkrumbeiha@ucdavis.edu
                cgiulivi@ucdavis.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 October 2023
                24 October 2023
                2023
                : 13
                : 18129
                Affiliations
                [1 ]Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, ( https://ror.org/05rrcem69) Davis, CA USA
                [2 ]Medical Investigation of Neurodevelopmental Disorders (MIND) Institute UCDH, University of California Davis, ( https://ror.org/05rrcem69) Sacramento, CA USA
                Article
                44807
                10.1038/s41598-023-44807-y
                10598273
                37875542
                b190b202-30ea-4cd7-a179-ac3700cfc697
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 August 2023
                : 12 October 2023
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                © Springer Nature Limited 2023

                Uncategorized
                imaging,cellular neuroscience
                Uncategorized
                imaging, cellular neuroscience

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