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Lysosomes signal through the epigenome to regulate longevity across generations [I]

ABSTRACT: Lysosomes signal through the epigenome to regulate longevity across generations [I]

PROVIDER: PRJNA987511 | ENA |

REPOSITORIES: ENA

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Lysosomes signal through the epigenome to regulate longevity across generations [III]

Project description:Lysosomes signal through the epigenome to regulate longevity across generations [III]

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Lysosomes signal through the epigenome to regulate longevity across generations [II]

Project description:Lysosomes signal through the epigenome to regulate longevity across generations [II]

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Lysosomes signal through the epigenome to regulate longevity across generations [III]

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Lysosomes signal through the epigenome to regulate longevity across generations [II]

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Lysosomes signal through the epigenome to regulate longevity across generations [I]

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Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity

Project description:Lysosomes are active sites to integrate cellular metabolism and signal transduction. A collection of proteins enriched at lysosomes mediate these metabolic and signaling functions. Both lysosomal metabolism and lysosomal signaling have been linked with longevity regulation; however, how lysosomes adjust their protein composition to accommodate this regulation remains unclear. Using large-scale proteomic profiling, we systemically profiled lysosome-enriched proteomes in association with different longevity mechanisms. We further discovered the lysosomal recruitment of AMPK and nucleoporin proteins and their requirements for longevity in response to increased lysosomal lipolysis. Through comparative proteomic analyses of lysosomes from different tissues and labeled with different markers, we discovered lysosomal heterogeneity across tissues as well as the specific enrichment of the Ragulator complex on Cystinosin positive lysosomes. Together, this work uncovers lysosomal proteome heterogeneity at different levels and provides resources for understanding the contribution of lysosomal proteome dynamics in modulating signal transduction, organelle crosstalk and organism longevity.

2023-11-11 | MSV000093375 | MassIVE

Organelle proteomic profiling reveals lysosomal heterogeneity in association with longevity

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Lysosome Lipid Signaling from the Periphery to Neurons Regulates Longevity

Project description:<p>Lysosomes are key cellular organelles that metabolize extra- and intra-cellular substrates. Alterations in lysosomal metabolism are implicated in aging-associated metabolic and neurodegenerative diseases. However, how lysosomal metabolism actively coordinates the metabolic and nervous systems to regulate aging remains unclear. Here, we report a fat-to-neuron lipid signaling pathway induced by lysosomal metabolism and its longevity promoting role in <em>Caenorhabditis elegans</em>. We discovered that induced lysosomal lipolysis in peripheral fat storage tissue up-regulates the neuropeptide signaling pathway in the nervous system to promote longevity. This cell-non-autonomous regulation is mediated by a 47 specific polyunsaturated fatty acid, dihomo-gamma-linolenic acid (DGLA) and LBP-3 lipid chaperone protein transporting from the fat storage tissue to neurons. LBP-3 binds to DGLA, and acts through NHR-49 nuclear receptor and NLP-11 neuropeptide in neurons to extend lifespan. These results reveal lysosomes as a signaling hub to coordinate metabolism and aging, and lysosomal signaling mediated inter-tissue communication in promoting longevity.</p>

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Peripheral positioning of lysosomes supports melanoma aggressiveness

Project description:Emerging evidences suggest that both function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how lysosomes function is linked to their position and thereby control metastatic progression remains elusive. Here, we analyzed lysosome subcellular distribution in micropatterned patient-derived melanoma cells and found that lysosome spreading scales with their aggressiveness. Peripheral lysosomes promote invadopodia-based matrix degradation and invasion of melanoma cells which is directly linked to their lysosomal and cell transcriptional programs. When controlling lysosomal positioning using chemo-genetical heterodimerization in melanoma cells, we demonstrated that perinuclear clustering impairs lysosomal secretion, matrix degradation and invasion. Impairing lysosomal spreading in a zebrafish metastasis model significantly reduces invasive outgrowth. Our study provides a mechanistic demonstration that lysosomal positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis.

2023-07-31 | E-MTAB-13165 | biostudies-arrayexpress

Epigenome

Project description:Epigenome

2022-03-31 | OEX00016373 | NODE