Endolysosomal processing of neuron-derived signaling lipids regulates autophagy and lipid droplet degradation in astrocytes DOI Creative Commons
Jagannatham Naidu Bhupana,

Angelid Pabon,

Ho Hang Leung

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract Astrocytes support brain metabolism by processing, storing, and appropriating metabolites. Dynamic regulation of metabolic activities in astrocytes is critical to meeting the demands other cells. During neuronal stress, lipid metabolites are transferred from neurons astrocytes, where they stored droplets (LDs). However, it not clear whether how neuron-derived lipids trigger adaptation astrocytes. Here, we uncover an endolysosomal function that mediates a neuron-astrocyte transcellular signaling paradigm. We identify Tweety homolog 1 (TTYH1) as astrocyte-enriched transmembrane protein localized endolysosomes, facilitates autophagic flux droplet (LD) degradation. Astrocyte-specific deletion Ttyh1 mice loss TTYH1 ortholog Drosophila lead accumulation neutral lipids. Computational experimental evidence suggests clearance ceramide 1-phosphate (C1P), sphingolipid dampens LD breakdown mouse human found inflammatory cytokine IL-1β induces upregulation C1P biosynthesis. Concurrently, secreted cause impairment Whereas deficiency exacerbates catabolic blockage, inhibiting synthesis restores normalizes contents Thus, rely on mitigate effects Taken together, our findings reveal neuron-initiated paradigm culminates

Language: Английский

Endolysosomal processing of neuron-derived signaling lipids regulates autophagy and lipid droplet degradation in astrocytes DOI Creative Commons
Jagannatham Naidu Bhupana,

Angelid Pabon,

Ho Hang Leung

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 31, 2025

Language: Английский

Citations

0
Crosstalk between degradation and bioenergetics: how autophagy and endolysosomal processes regulate energy production DOI Creative Commons

Angelid Pabon,

Jagannatham Naidu Bhupana, Ching‐On Wong

et al.

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(3), P. 671 - 681

Published: May 10, 2024

Cells undergo metabolic reprogramming to adapt changes in nutrient availability, cellular activity, and transitions cell states. The balance between glycolysis mitochondrial respiration is crucial for energy production, stipulates a shift such optimize both bioenergetic efficiency anabolic requirements. Failure switching dependence can lead maladaptation pathogenesis. While degradation known recycle precursor molecules anabolism, its potential role regulating production remains less explored. switch involves transcription factors organelle homeostasis, which are regulated by the pathways. A growing body of studies has demonstrated that stem cells differentiated exhibit upon perturbations autophagic activity or endolysosomal processes. Here, we highlighted current understanding interplay processes, specifically autophagy endolysosomes, factors, signaling, homeostasis shaping bioenergetics. This review aims summarize relationship processes bioenergetics, providing foundation future research unveil deeper mechanistic insights into regulation.

Language: Английский

Citations

1
Endolysosomal processing of neuron-derived signaling lipids regulates autophagy and lipid droplet degradation in astrocytes DOI Creative Commons
Jagannatham Naidu Bhupana,

Angelid Pabon,

Ho Hang Leung

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract Astrocytes support brain metabolism by processing, storing, and appropriating metabolites. Dynamic regulation of metabolic activities in astrocytes is critical to meeting the demands other cells. During neuronal stress, lipid metabolites are transferred from neurons astrocytes, where they stored droplets (LDs). However, it not clear whether how neuron-derived lipids trigger adaptation astrocytes. Here, we uncover an endolysosomal function that mediates a neuron-astrocyte transcellular signaling paradigm. We identify Tweety homolog 1 (TTYH1) as astrocyte-enriched transmembrane protein localized endolysosomes, facilitates autophagic flux droplet (LD) degradation. Astrocyte-specific deletion Ttyh1 mice loss TTYH1 ortholog Drosophila lead accumulation neutral lipids. Computational experimental evidence suggests clearance ceramide 1-phosphate (C1P), sphingolipid dampens LD breakdown mouse human found inflammatory cytokine IL-1β induces upregulation C1P biosynthesis. Concurrently, secreted cause impairment Whereas deficiency exacerbates catabolic blockage, inhibiting synthesis restores normalizes contents Thus, rely on mitigate effects Taken together, our findings reveal neuron-initiated paradigm culminates

Language: Английский

Citations

0