The Lipid Droplet and the Endoplasmic Reticulum

Ohsaki, Yuki; Sołtysik, Kamil; Fujimoto, Toyoshi

doi:10.1007/978-981-10-4567-7_8

Cited by 19 publications

(14 citation statements)

References 72 publications

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“…Cytosolic LDs bud from ER monolayer leaflets 42‐44 . In order to study the effect of DRP1 on dynamics of LD formation in ER, we pulse‐chased fresh sWAT explants from cold‐exposed Adipo‐ Drp1 flx/flx and control mice with fluorescent labeled long‐chain fatty acid BODIPY‐C 12 (red) 38 followed by co‐staining with ER tracker (green) (Figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Yang

Mao

et al. 2020

FASEB j.

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Dynamin‐Related‐Protein 1 (DRP1) critically regulates mitochondrial and peroxisomal fission in multicellular organisms. However, the impact of DRP1 on other organelles, especially its direct influence on ER functions remains largely unclear. Here, we report that DRP1 translocates to endoplasmic reticulum (ER) in response to β‐adrenergic stimulation. To further investigate the function of DRP1 on ER‐lipid droplet (LD) dynamics and the metabolic subsequences, we generated an adipose tissue‐specific DRP1 knockout model (Adipo‐Drp1flx/flx). We found that the LDs in adipose tissues of Adipo‐Drp1flx/flx mice exhibited more unilocular morphology with larger sizes, and formed less multilocular structures upon cold exposure. Mechanistically, we discovered that abnormal LD morphology occurs because newly generated micro‐LDs fail to dissociate from the ER due to DRP1 ablation. Conversely, the ER retention of LDs can be rescued by the overexpressed DRP1 in the adipocytes. The alteration of LD dynamics, combined with abnormal mitochondrial and autophagy functions in adipose tissue, ultimately lead to abnormalities in lipid metabolism in Adipo‐Drp1flx/flx mice.

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Section: Resultsmentioning

confidence: 99%

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Yang

Mao

et al. 2020

FASEB j.

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“…Both LDs and peroxisomes, with roles in lipid storage and lipid degradation respectively, can be generated from ER (Joshi et al, 2018). Moreover, the distribution and function of these two organelles depend on their contacts with ER (Ohsaki et al, 2017;Farré et al, 2018). ER-peroxisome contacts can be mediated by VAP proteins and the endosomal-associated protein acylcoenzyme A-binding domain protein 5 (ACBD5) (Costello et al, 2017;Hua et al, 2017).…”

Section: Er Mcs and Intracellular Membrane Traffickingmentioning

confidence: 99%

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

2020

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The physical continuity of axons over long cellular distances poses challenges for their maintenance. One organelle that faces this challenge is endoplasmic reticulum (ER); unlike other intracellular organelles, this forms a physically continuous network throughout the cell, with a single membrane and a single lumen. In axons, ER is mainly smooth, forming a tubular network with occasional sheets or cisternae and low amounts of rough ER. It has many potential roles: lipid biosynthesis, glucose homeostasis, a Ca 2+ store, protein export, and contacting and regulating other organelles. This tubular network structure is determined by ER-shaping proteins, mutations in some of which are causative for neurodegenerative disorders such as hereditary spastic paraplegia (HSP). While axonal ER shares many features with the tubular ER network in other contexts, these features must be adapted to the long and narrow dimensions of axons. ER appears to be physically continuous throughout axons, over distances that are enormous on a subcellular scale. It is therefore a potential channel for long-distance or regional communication within neurons, independent of action potentials or physical transport of cargos, but involving its physiological roles such as Ca 2+ or organelle homeostasis. Despite its apparent stability, axonal ER is highly dynamic, showing features like anterograde and retrograde transport, potentially reflecting continuous fusion and breakage of the network. Here we discuss the transport processes that must contribute to this dynamic behavior of ER. We also discuss the model that these processes underpin a homeostatic process that ensures both enough ER to maintain continuity of the network and repair breaks in it, but not too much ER that might disrupt local cellular physiology. Finally, we discuss how failure of ER organization in axons could lead to axon degenerative diseases, and how a requirement for ER continuity could make distal axons most susceptible to degeneration in conditions that disrupt ER continuity.

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“…In yeast and several mammalian cell types, LDs appear to retain a functional connectivity with the ER (Jacquier et al, 2011;Salo et al, 2016;Wilfling et al, 2013). Considering the mounting evidence for membrane continuities between the ER and LDs, there are likely machineries that control these contacts and regulate LD growth (Ohsaki et al, 2017;Salo and Ikonen, 2019;Schuldiner and Bohnert, 2017). Seipin, a homo-oligomeric ER transmembrane protein that localizes to ER-LD contacts, may be part of such machinery (Binns et al, 2010;Fei et al, 2008;Salo et al, 2016;Szymanski et al, 2007;Wang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Seipin Facilitates Triglyceride Flow to Lipid Droplet and Counteracts Droplet Ripening via Endoplasmic Reticulum Contact

et al. 2019

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Graphical AbstractHighlights d Seipin can determine the site of LD formation d Seipin-mediated ER-LD membrane contacts display a uniform neck-like architecture d Seipin at ER-LD contact facilitates continuous triglyceride transfer to LD d Acute removal of seipin reveals a principle of LD ripening via the ER SUMMARY Seipin is an oligomeric integral endoplasmic reticulum (ER) protein involved in lipid droplet (LD) biogenesis. To study the role of seipin in LD formation, we relocalized it to the nuclear envelope and found that LDs formed at these new seipin-defined sites. The sites were characterized by uniform seipinmediated ER-LD necks. At low seipin content, LDs only grew at seipin sites, and tiny, growth-incompetent LDs appeared in a Rab18-dependent manner. When seipin was removed from ER-LD contacts within 1 h, no lipid metabolic defects were observed, but LDs became heterogeneous in size. Studies in seipin-ablated cells and model membranes revealed that this heterogeneity arises via a biophysical ripening process, with triglycerides partitioning from smaller to larger LDs through droplet-bilayer contacts. These results suggest that seipin supports the formation of structurally uniform ER-LD contacts and facilitates the delivery of triglycerides from ER to LDs. This counteracts ripening-induced shrinkage of small LDs.

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The Lipid Droplet and the Endoplasmic Reticulum

Cited by 19 publications

References 72 publications

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration

Seipin Facilitates Triglyceride Flow to Lipid Droplet and Counteracts Droplet Ripening via Endoplasmic Reticulum Contact

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