Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy

Ouahoud, Sarah; Fiet, Mitchell D; Martínez-Montañés, Fernando; Ejsing, Christer S.; Kuß, Oliver; Roden, Michael; Markgraf, Daniel F.

doi:10.1242/jcs.213876

Cited by 25 publications

(27 citation statements)

References 87 publications

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“…To determine whether TAG lipolysis is indeed required for the formation of DAG microdomains during growth resumption, we monitored the distribution of cytosolic DAG pools in cells lacking TAG lipases. Tgl3 is an LD‐associated lipase that mediates TAG lipolysis during re‐entry of growth in S. cerevisiae . It has been shown that in the absence of the vacuolar lipase Atg15 ( atg15 Δ), Tgl3 and another LD‐associated lipase, Tgl4, become hyperactive, leading to enhanced lipolysis .…”

Section: Resultsmentioning

confidence: 99%

“…Tgl3 is an LD-associated lipase that mediates TAG lipolysis during re-entry of growth in S. cerevisiae. 63 It has been shown that in the absence of the vacuolar lipase Atg15 (atg15Δ), Tgl3 and another LD-associated lipase, Tgl4, become hyperactive, leading to enhanced lipolysis. 64 In fact, vacuolar DAG microdomains were abundant in cells lacking Atg15, where Tgl3 and Tgl4 activity is enhanced ( Figure 2).…”

Section: Dag Microdomains Are Formed In the Yeast Vacuole During Grmentioning

confidence: 99%

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Metabolic control of cytosolic‐facing pools of diacylglycerol in budding yeast

Ganesan

Ponce

Tavassoli

et al. 2019

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Diacylglycerol (DAG) is a key signaling lipid and intermediate in lipid metabolism. Our knowledge of DAG distribution and dynamics in cell membranes is limited. Using live‐cell fluorescence microscopy we investigated the localization of yeast cytosolic‐facing pools of DAG in response to conditions where lipid homeostasis and DAG levels were known to be altered. Two main pools were monitored over time using DAG sensors. One pool was associated with vacuolar membranes and the other localized to sites of polarized growth. Dynamic changes in DAG distribution were observed during resumption of growth from stationary phase, when DAG is used to support phospholipid synthesis for membrane proliferation. Vacuolar membranes experienced constant morphological changes displaying DAG enriched microdomains coexisting with liquid‐disordered areas demarcated by Vph1. Formation of these domains was dependent on triacylglycerol (TAG) lipolysis. DAG domains and puncta were closely connected to lipid droplets. Lack of conversion of DAG to phosphatidate in growth conditions dependent on TAG mobilization, led to the accumulation of DAG in a vacuolar‐associated compartment, impacting the polarized distribution of DAG at budding sites. DAG polarization was also regulated by phosphatidylserine synthesis/traffic and sphingolipid synthesis in the Golgi.

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Section: Resultsmentioning

confidence: 99%

Section: Dag Microdomains Are Formed In the Yeast Vacuole During Grmentioning

confidence: 99%

Metabolic control of cytosolic‐facing pools of diacylglycerol in budding yeast

Ganesan

Ponce

Tavassoli

et al. 2019

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“…A subset of ESCRT components function in other pathways inside the cell. These include lipid droplet consumption ( Ouahoud et al. , 2018 ), peroxisome scission ( Mast et al.…”

Section: Discussionmentioning

confidence: 99%

ESCRT-III and ER–PM contacts maintain lipid homeostasis

Jorgensen

Tei

Baskin

et al. 2020

MBoC

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“…Such feedback mechanisms have not been considered here, but could be included in future studies. Similarly, transport and metabolism of sterols and other lipids can change throughout the yeast cell cycle, for example prior to and after diauxic shift or during growth resumption and in the stationary state [85, 86]. Also, steryl esters in LDs can be utilized by other pathways, such as by ingestion into the vacuole (the yeast lysosome) during starvation in a process called lipophagy [87, 88].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Steady state analysis of influx and transbilayer distribution of ergosterol in the yeast plasma membrane

Wüstner

2019

Theor Biol Med Model

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Background The transbilayer sterol distribution between both plasma membrane (PM) leaflets has long been debated. Recent studies in mammalian cells and in yeast show that the majority of sterol resides in the inner PM leaflet. Since sterol flip-flop in model membranes is rapid and energy-independent, a mechanistic understanding for net enrichment of sterol in one leaflet is lacking. Import of ergosterol in yeast can take place via the ABC transporters Aus1/Pdr11 under anaerobic growth conditions, eventually followed by rapid non-vesicular sterol transport to the endoplasmic reticulum (ER). Little is known about how these transport steps are dynamically coordinated. Methods Here, a kinetic steady state model is presented which considers sterol import via Aus1/Pdr11, sterol flip-flop across the PM, bi-molecular complex formation and intracellular sterol release followed by eventual transport to and esterification of sterol in the ER. The steady state flux is calculated, and a thermodynamic analysis of feasibility is presented. Results It is shown that the steady state sterol flux across the PM can be entirely controlled by irreversible sterol import via Aus1/Pdr11. The transbilayer sterol flux at steady state is a non-linear function of the chemical potential difference of sterol between both leaflets. Non-vesicular release of sterol on the cytoplasmic side of the PM lowers the attainable sterol enrichment in the inner leaflet. Including complex formation of sterol with phospholipids or proteins can explain several puzzling experimental observations; 1) rapid sterol flip-flop across the PM despite net sterol enrichment in one leaflet, 2) a pronounced steady state sterol gradient between PM and ER despite fast non-vesicular sterol exchange between both compartments and 3) a non-linear dependence of ER sterol on ergosterol abundance in the PM. Conclusions A steady state model is presented that can account for the observed sterol asymmetry in the yeast PM, the strong sterol gradient between PM and ER and threshold-like expansion of ER sterol for increasing sterol influx into the PM. The model also provides new insight into selective uptake of cholesterol and its homeostasis in mammalian cells, and it provides testable predictions for future experiments.

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Lipid droplet consumption is functionally coupled to vacuole homeostasis independent of lipophagy

Cited by 25 publications

References 87 publications

Metabolic control of cytosolic‐facing pools of diacylglycerol in budding yeast

Metabolic control of cytosolic‐facing pools of diacylglycerol in budding yeast

ESCRT-III and ER–PM contacts maintain lipid homeostasis

Steady state analysis of influx and transbilayer distribution of ergosterol in the yeast plasma membrane

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