The pathogenesis of Parkinson's disease

The Lancet, Journal Year: 2024, Volume and Issue: 403(10423), P. 293 - 304

Published: Jan. 1, 2024

Language: Английский

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ER-mitochondria contact sites; a multifaceted factory for Ca2+ signaling and lipid transport

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 16, 2022

Membrane contact sites (MCS) between organelles of eukaryotic cells provide structural integrity and promote organelle homeostasis by facilitating intracellular signaling, exchange ions, metabolites lipids membrane dynamics. Cataloguing MCS revolutionized our understanding the organization a cell, but functional role MSCs their in complex diseases, such as cancer, are only gradually emerging. In particular, endoplasmic reticulum (ER)-mitochondria contacts (EMCS) key effectors non-vesicular lipid trafficking, thereby regulating composition cellular membranes organelles, physiological functions lipid-mediated signaling pathways both diseased conditions. this short review, we discuss aspects complexity EMCS mammalian cells, with particular emphasis on central hubs for transport these how perturbations may favor traits cancer cells.

Language: Английский

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Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(8), P. 1157 - 1172

Published: July 3, 2023

Lipid mobilization through fatty acid β-oxidation is a central process essential for energy production during nutrient shortage. In yeast, this catabolic starts in the peroxisome from where products enter mitochondria and fuel tricarboxylic cycle. Little known about physical metabolic cooperation between these organelles. Here we found that expression of transporters rate-limiting enzyme involved decreased cells expressing hyperactive mutant small GTPase Arf1, leading to an accumulation acids lipid droplets. Consequently, became fragmented ATP synthesis decreased. Genetic pharmacological depletion phenocopied arf1 mitochondrial phenotype. Although occurs both peroxisomes mammals, Arf1's role metabolism conserved. Together, our results indicate Arf1 integrates into by regulating storage utilization, presumably organelle contact sites.

Language: Английский

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Functional interplay of lipid droplets and mitochondria

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(10), P. 1235 - 1251

Published: Jan. 24, 2024

Our body stores energy mostly in form of fatty acids (FAs) lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes mitochondria. This transfer is dependent on close opposition LDs mitochondria happens at membrane contact sites. However, composition dynamics these sites not well understood, which part due dependence metabolic state cell cell- tissue-type. Here, we summarize current knowledge contacts between both mammals yeast Saccharomyces cerevisiae, various are studied. We discuss possible functions site their implication disease.

Language: Английский

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Parkinson’s disease-associated Pink1 loss disrupts vesicle trafficking in Ensheathing glia causing dopaminergic neuron synapse loss

Published: Feb. 17, 2025

Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in substantia nigra , but many other cell types are affected even before neuron occurs. Recent studies have linked oligodendrocytes to early stages PD, though their precise role still unclear. Pink1 mutated familial PD and through unbiased single-cell sequencing entire brain Drosophila models, we observed significant gene deregulation ensheathing glia (EG); cells that share functional similarities oligodendrocytes. We found leads activation EG, similar reactive response EG seen upon nerve injury. Using cell-type specific transcriptomics, identified deregulated genes as potential modifiers. Specifically, downregulating two trafficking factors, Rab7 Vps13, also or direct regulators Rab7, Mon1 Ccz1, specifically was sufficient rescue neuronal function protect against synapse loss. Our findings demonstrate triggers an injury turn disrupts function. Vesicle components, which regulate membrane interactions between organelles within play a crucial maintaining health preventing work highlights essential glial support pathogenesis identifies vesicle these key point convergence progression.

Language: Английский

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Mitochondrial dysfunction, oxidative stress, ER stress and mitochondria-ER crosstalk alterations in a chemical rat model of Huntington's disease: Potential benefits of bezafibrate

Toxicology Letters, Journal Year: 2023, Volume and Issue: 381, P. 48 - 59

Published: April 26, 2023

Language: Английский

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Mitochondria-ER contact sites expand during mitosis

iScience, Journal Year: 2024, Volume and Issue: 27(4), P. 109379 - 109379

Published: March 1, 2024

Language: Английский

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Lipid Droplet–Mitochondria Contacts in Health and Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 6878 - 6878

Published: June 22, 2024

The orchestration of cellular metabolism and redox balance is a complex, multifaceted process crucial for maintaining homeostasis. Lipid droplets (LDs), once considered inert storage depots neutral lipids, are now recognized as dynamic organelles critical in lipid energy regulation. Mitochondria, the powerhouses cell, play central role production, metabolic pathways, signaling. physical functional contacts between LDs mitochondria facilitate direct transfer primarily fatty acids, which mitochondrial β-oxidation, thus influencing homeostasis health. This review highlights recent advances understanding mechanisms governing LD-mitochondria interactions their regulation, drawing attention to proteins pathways that mediate these contacts. We discuss physiological relevance interactions, emphasizing within cells, how processes response demands stress conditions. Furthermore, we explore pathological implications dysregulated particularly context diseases such obesity, diabetes, non-alcoholic liver disease, potential links cardiovascular neurodegenerative diseases. Conclusively, this provides comprehensive overview current underscoring significance suggesting future research directions could unveil novel therapeutic targets degenerative

Language: Английский

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Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(9), P. 6528 - 6538

Published: Feb. 6, 2024

Language: Английский

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Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(5)

Published: May 21, 2024

Abstract Seipin is one key mediator of lipid metabolism that highly expressed in adipose tissues as well the brain. Lack gene, Bscl2 , leads to not only severe metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly lipids, facilitates nerve transmission important for coordination learning. Whether deficiency-leaded defects learning underlined by dysregulation its consequent myelin abnormalities remains be elucidated. In present study, we verified expression oligodendrocytes (OLs) their precursors, oligodendrocyte precursor cells (OPCs), demonstrated deficiency compromised OPC differentiation, which led decreased OL numbers, protein, myelinated fiber proportion thickness myelin. Deficiency resulted impaired spatial cognition mice. Mechanistically, suppressed sphingolipid metabolism-related genes OPCs caused morphological droplets (LDs), markedly impeded differentiation. Importantly, rosiglitazone, agonist PPAR-gamma, substantially restored phenotypes resulting from deficiency, such aberrant LDs, reduced sphingolipids, obstructed neurobehavioral defects. Collectively, study elucidated how deficiency-induced deficits via impairing myelination, may pave way developing novel intervention strategy treating metabolism-involved neurological disorders.

Language: Английский

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