Cell-specific mitochondrial response in progressive supranuclear palsy

Mitochondrion, Journal Year: 2025, Volume and Issue: unknown, P. 102043 - 102043

Published: April 1, 2025

Progressive supranuclear palsy (PSP) is a main form of idiopathic tauopathy characterized neuropathologically by subcortical neurofibrillary tangles in neurons, oligodendroglial coiled bodies, and tufted astrocytes, which follow sequential distribution the human brain. Mitochondrial dysfunction thought to be contributor many neurodegenerative diseases, but its role PSP at cellular level remains incompletely understood. To address this, we performed cell-specific morphometric analysis mitochondrial markers post-mortem tissues from motor cortex patients non-diseased controls (n = 5 each) followed single-nuclear transcriptomics 3 identify changes genes that regulate function. We treated iCell astrocytes with brain homogenates isolated viable multiple regions PSP-affected brains. found significant neurons immunohistochemical level, particularly complex I, distinct transcriptomic responses across cell types. Glial cells exhibited upregulation pathways associated In contrast, excitatory inhibitory showed downregulation these pathways, indicating impaired Astrocytes derived different express varied levels GFAP EAAT1 immunoreactivity. Astrocytic tau pathology culture postmortem brains mirrors seen corresponding tissue histology. Tau astrocyte clumps mitochondria potentially impairment their neuron supportive Our results underscore selective I damage cell-type specific patterns differentiate other diseases.

Language: Английский

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Mitophagy in Neurons: Mechanisms Regulating Mitochondrial Turnover and Neuronal Homeostasis

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169161 - 169161

Published: April 1, 2025

Language: Английский

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Mechanical force of uterine occupation enables large vesicle extrusion from proteostressed maternal neurons

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 19, 2024

Large vesicle extrusion from neurons may contribute to spreading pathogenic protein aggregates and promoting inflammatory responses, two mechanisms leading neurodegenerative disease. Factors that regulate the of large vesicles, such as exophers produced by proteostressed C. elegans touch neurons, are poorly understood. Here, we document mechanical force can significantly potentiate exopher neurons. Exopher production ALMR neuron peaks at adult day 2 or 3, coinciding with reproductive peak. Genetic disruption germline, sperm, oocytes, egg/early embryo strongly suppress during peak period. Conversely, restoring egg late phase through mating males inducing retention via genetic interventions block egg-laying increase production. Overall, promote associated expanded uterus lengths shorter lengths. In addition impact fertilized eggs, be enhanced filling dead even fluid, supporting distention consequences, rather than presence constitute exopher-inducing stimulus. We conclude uterine occupation potentiates proximal maternal Our observations draw attention potential importance signaling in extracellular aggregate mechanisms, making a case for mechanobiology

Language: Английский

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Exploring the limitations of mitochondrial dye as a genuine horizontal mitochondrial transfer surrogate

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 7, 2024

Abstract Rosamine-based mitochondrial dyes, such as Mitotracker Red, have commonly been employed to visualize localization within cells due their preferential accumulation in organelles with membrane potential. Consequently, Red has often served a surrogate indicator for tracking movement between neighboring cells. However, it is important note that the presence of potential cell and other may lead non-specific partial enrichment locations than mitochondria. This study comprehensively investigates reliability dye marker studying horizontal transfer (HMT). By meticulous replicating previous experiments comparing efficiency mito-targeted GFP, our findings confirm HMT occurs at significantly lower previously indicated by dye. Subsequent involving mitochondria-deficient robustly demonstrates non-specificity We advocate thorough reevaluation existing literature this field propose exploration alternative techniques enhance investigation HMT. addressing these pivotal aspects, we can advance understanding cellular dynamics pave way future explorations captivating field.

Language: Английский

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Mitochondrial calcium signaling in non-neuronal cells: Implications for Alzheimer's disease pathogenesis

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167169 - 167169

Published: April 15, 2024

Language: Английский

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