The role of ceramide in regulating endoplasmic reticulum function

Zelnik, Iris Daphne; Ventura, Ana E.; Kim, Jiyoon L.; Silva, Liana C.; Futerman, Anthony H.

doi:10.1016/j.bbalip.2019.06.015

Cited by 35 publications

(28 citation statements)

References 87 publications

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“…From these dihydroceramides the enzyme dihydroceramide desaturase-1 (DES1) forms Cer. The primary sphingolipid Cer is subject to further metabolism and its levels are tightly controlled in this manner, a necessity for cells since Cer promotes concentration-dependently apoptotic processes, and subsequent cell death (Zelnik et al, 2019). Cer may be converted into sphingomyelin (SM; phosphocholine-ceramide) or ceramide-1-phosphate (Cer1P).…”

Section: Introduction To Glycosphingolipidsmentioning

confidence: 99%

Glycosphingolipids and Infection. Potential New Therapeutic Avenues

Aerts

Artola

Eijk

et al. 2019

Front. Cell Dev. Biol.

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Glycosphingolipids (GSLs), the main topic of this review, are a subclass of sphingolipids. With their glycans exposed to the extracellular space, glycosphingolipids are ubiquitous components of the plasma membrane of cells. GSLs are implicated in a variety of biological processes including specific infections. Several pathogens use GSLs at the surface of host cells as binding receptors. In addition, lipid-rafts in the plasma membrane of host cells may act as platform for signaling the presence of pathogens. Relatively common in man are inherited deficiencies in lysosomal glycosidases involved in the turnover of GSLs. The associated storage disorders (glycosphingolipidoses) show lysosomal accumulation of substrate(s) of the deficient enzyme. In recent years compounds have been identified that allow modulation of GSLs levels in cells. Some of these agents are well tolerated and already used to treat lysosomal glycosphingolipidoses. This review summarizes present knowledge on the role of GSLs in infection and subsequent immune response. It concludes with the thought to apply glycosphingolipid-lowering agents to prevent and/or combat infections.

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Section: Introduction To Glycosphingolipidsmentioning

confidence: 99%

Glycosphingolipids and Infection. Potential New Therapeutic Avenues

Aerts

Artola

Eijk

et al. 2019

Front. Cell Dev. Biol.

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“…These phospholipids, which are particularly important to define membrane fluidity, may participate in ER shaping and organelle contact. PEs are also chaperone lipids that ensure protein folding and participate in ER stress [68,69]. These findings show that Spastin functions are linked with the modulation of the lipid profile in neuronal and muscle tissues.…”

Section: Spastin Coordinates Mts and Er Shaping To Modulate Lds Dispementioning

confidence: 91%

“…Altogether, these finding confirmed the impact of Spastin on structural lipids with organ specificities. Interestingly, Spastin affected particularly PE and Cer, two major components of organelle membranes known to impact membrane fluidity and folding, notably in the ER [68,69].…”

Section: Plos Geneticsmentioning

confidence: 99%

Spastin mutations impair coordination between lipid droplet dispersion and reticulum

et al. 2020

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Lipid droplets (LD) are affected in multiple human disorders. These highly dynamic organelles are involved in many cellular roles. While their intracellular dispersion is crucial to ensure their function and other organelles-contact, underlying mechanisms are still unclear. Here we show that Spastin, one of the major proteins involved in Hereditary Spastic Paraplegia (HSP), controls LD dispersion. Spastin depletion in zebrafish affects metabolic properties and organelle dynamics. These functions are ensured by a conserved complex set of splice variants. M1 isoforms determine LD dispersion in the cell by orchestrating endoplasmic reticulum (ER) shape along microtubules (MTs). To further impact LD fate, Spastin modulates transcripts levels and subcellular location of other HSP key players, notably Seipin and REEP1. In pathological conditions, mutations in human Spastin M1 disrupt this mechanism and impacts LD network. Spastin depletion influences not only other key proteins but also modulates specific neutral lipids and phospholipids, revealing an impact on membrane and organelle components. Altogether our results show that Spastin and its partners converge in a common machinery that coordinates LD dispersion and ER shape along MTs. Any alteration of this system results in HSP clinical features and impacts lipids profile, thus opening new avenues for novel biomarkers of HSP.

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“…1 Ceramides are minor components of cell membranes' differentiation and senescence and involved in cellular stress response and growth. 2 Moreover, it was found that ceramides can serve as prognostic biomarkers in acute myocardial infarction, 3 cancer, 4,5 diabetes, 6 and Alzheimer's disease. 7 The recent evidence demonstrates that C 18 -ceramide is linked to the establishment of insulin resistance in human skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

“…The determination of ceramides' levels has gained much interest because of their significant role in various cellular functions 1 . Ceramides are minor components of cell membranes' differentiation and senescence and involved in cellular stress response and growth 2 . Moreover, it was found that ceramides can serve as prognostic biomarkers in acute myocardial infarction, 3 cancer, 4,5 diabetes, 6 and Alzheimer's disease 7 .…”

Section: Introductionmentioning

confidence: 99%