Lysosomal damage sensing and lysophagy initiation by SPG20-ITCH

Molecular Cell, Год журнала: 2024, Номер 84(8), С. 1556 - 1569.e10

Опубликована: Март 18, 2024

Cells respond to lysosomal membrane permeabilization by repair or selective macroautophagy of damaged lysosomes, termed lysophagy, but it is not fully understood how this decision made. Here, we uncover a pathway in human cells that detects lipid bilayer perturbations the limiting compromised which fail be repaired, and then initiates ubiquitin-triggered lysophagy. We find SPG20 binds factor IST1 on lysosomes and, importantly, integrates with detection damage-associated lipid-packing defects membrane. Detection occurs via sensory amphipathic helices before rupture If are extensive, such as during peroxidation, recruits activates ITCH, marks lysosome lysine-63-linked ubiquitin chains initiate lysophagy thus triages for destruction. With being linked neurodegeneration, these findings highlight relevance coordinated damage response cellular homeostasis.

Язык: Английский

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Emerging functions of the mitochondria–ER–lipid droplet three‐way junction in coordinating lipid transfer, metabolism, and storage in cells

FEBS Letters, Год журнала: 2024, Номер 598(10), С. 1252 - 1273

Опубликована: Май 1, 2024

Over the past two decades, we have witnessed a growing appreciation for importance of membrane contact sites (CS) in facilitating direct communication between organelles. CS are tiny regions where membranes organelles meet but do not fuse and allow transfer metabolites organelles, playing crucial roles coordination cellular metabolic activities. The significant advancements imaging techniques molecular cell biology research revealed that more complex than what originally thought, as they extremely dynamic, can remodel their shape, composition, functions accordance with environmental changes occur Here, describe how recent studies led to identification three-way mitochondria-ER-lipid droplet discuss emerging these contacts maintaining lipid storage, homeostasis, balance. We also summarize properties key protein components localized at interface, special focus on proteins. Understanding tripartite is essential unraveling complexities inter-organelle cooperation within cells.

Язык: Английский

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Specificity of lipid transfer proteins: an in vitro story

Biochimie, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Язык: Английский

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Mechanisms of lipid droplet degradation

Current Opinion in Cell Biology, Год журнала: 2024, Номер 90, С. 102402 - 102402

Опубликована: Июль 24, 2024

Язык: Английский

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Spartin is a Lipid Transfer Protein That Facilitates Lipid Droplet Turnover

Contact, Год журнала: 2024, Номер 7

Опубликована: Янв. 1, 2024

One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them autophagy. This process involves spartin, mutations of cause the rare inherited disorder Troyer syndrome (or spastic paraplegia-20, SPG20). A recently published paper from team led Karin Reinsich (Yale) suggests that molecular function spartin and its unique highly conserved “senescence” domain as a transfer protein. Spartin binds transfers all species found droplets, phospholipids triglycerides sterol esters. activity correlates with spartin's ability sustain droplet turnover. The senescence poses an intriguing question around wide range cargoes, but intriguingly it has yet yield up secrets because attempts at crystallization failed AlphaFold's prediction unconvincing.

Язык: Английский

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The membrane curvature-inducing REEP1-4 proteins generate an ER-derived vesicular compartment

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 5, 2024

Язык: Английский

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