CG32803 is the fly homolog of LDAF1 and influences lipid storage in vivo

Chartschenko, Eugenia; Hugenroth, Marie; Akhtar, Irfan; Droste, Andrea; Kolkhof, Petra; Bohnert, Maria; Beller, Mathias

doi:10.1016/j.ibmb.2020.103512

Cited by 6 publications

(7 citation statements)

References 43 publications

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“…LDAF1/promethin proteins are metazoan proteins with similarity to LDOs. These proteins also form a complex with seipin (Castro et al, 2019;Chartschenko et al, 2021;Chung et al, 2019), and their loss affects the process of LD biogenesis (Chung et al, 2019). It remains to be determined to which extent the multifunctional character that we observe for the yeast LDO proteins is conserved to metazoans, and whether these proteins have a role in lipid droplet turnover and/or contact sites.…”

Section: Discussionmentioning

confidence: 91%

“…These proteins are derived from overlapping genes, so that the smaller LDO variant Ldo16 is identical to the C-terminus of the longer Ldo45 (Figure 1A, bottom; Figure S1A) (Bohnert, 2020). LDAF1/promethin in humans and dmLDAF1 in fly are proteins with structural similarities to LDO, which also localize to LDs (Castro et al, 2019;Chartschenko et al, 2021;Chung et al, 2019). The LDO proteins as well as their putative metazoan counterparts LDAF1/promethin and dmLDAF1 are physically and functionally linked to seipin (Castro et al, 2019;Chartschenko et al, 2021;Chung et al, 2019), an evolutionarily conserved LD biogenesis machinery (Arlt et al, 2022;Fei et al, 2008;Grippa et al, 2015;Kim et al, 2022;Klug et al, 2021;Prasanna et al, 2021;Renne et al, 2022;Salo et al, 2016Salo et al, , 2019Sui et al, 2018;Szymanski et al, 2007;Wang et al, 2016;Yan et al, 2018;Zoni et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…LDAF1/promethin in humans and dmLDAF1 in fly are proteins with structural similarities to LDO, which also localize to LDs (Castro et al, 2019;Chartschenko et al, 2021;Chung et al, 2019). The LDO proteins as well as their putative metazoan counterparts LDAF1/promethin and dmLDAF1 are physically and functionally linked to seipin (Castro et al, 2019;Chartschenko et al, 2021;Chung et al, 2019), an evolutionarily conserved LD biogenesis machinery (Arlt et al, 2022;Fei et al, 2008;Grippa et al, 2015;Kim et al, 2022;Klug et al, 2021;Prasanna et al, 2021;Renne et al, 2022;Salo et al, 2016Salo et al, , 2019Sui et al, 2018;Szymanski et al, 2007;Wang et al, 2016;Yan et al, 2018;Zoni et al, 2021). Mutations in seipin result in Berardinelli Seip congenital generalized lipodystrophy type 2, and in neurological defects (Magré et al, 2001;Windpassinger et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Ldo45, but not Ldo16, is required for association of the phosphatidylinositol transfer protein (PITP) Pdr16 to the surface of these LDs (Eisenberg-Bord et al, 2018;Teixeira et al, 2018). Similarly, fly dmLDAF1 localizes to an LD subpopulation (Chartschenko et al, 2021). The LDO proteins are also involved in nutrient stress responses.…”

Section: Introductionmentioning

confidence: 99%

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A metabolically controlled contact site between lipid droplets and vacuoles

Diep

Collado

Hugenroth

et al. 2023

Preprint

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The lipid droplet (LD) organization proteins Ldo16 and Ldo45 affect multiple aspects of LD biology in yeast. They are linked to the LD biogenesis machinery seipin, and their loss causes defects in LD positioning, protein targeting, and breakdown. However, their molecular roles remained enigmatic. Here we report that Ldo16/45 form a tether-complex with Vac8 for creation of vacuole lipid droplet (vCLIP) contact sites, which can form in the absence of seipin. The phosphatidylinositol transfer protein Pdr16 is a further vCLIP-resident recruited by Ldo45. While only an LD-subpopulation is engaged in vCLIPs at glucose-replete conditions, nutrient stress results in vCLIP expansion, and vCLIP defects impair lipophagy upon prolonged starvation. In summary, Ldo16/45 are multifunctional proteins that orchestrate formation of a metabolically-regulated contact site. Our studies suggest an unexpected link between LD biogenesis and breakdown, and open the door to a deeper understanding of how lipid homeostasis is maintained during metabolic challenges.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A metabolically controlled contact site between lipid droplets and vacuoles

Diep

Collado

Hugenroth

et al. 2023

Preprint

Self Cite

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“…It is plausible that even in TAG-deprived situations minute amounts of TAGs may become stably clustered within the seipin disk, with a high number of seipin-LDAF1 complexes always primed for LD formation. In the absence of LDAF1, LDs are fewer in number but larger (Chung et al, 2019;Chartschenko et al, 2021), which could be a consequence of defectively primed ("TAGless") seipins needing higher ER TAG concentrations before LD formation can begin.…”

Section: Seipin Nucleates Ldsmentioning

confidence: 99%

Seipin—still a mysterious protein?

Salo

2023

Front. Cell Dev. Biol.

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Cells store excess energy in the form of lipid droplets (LDs), a specialized sub-compartment of the endoplasmic reticulum (ER) network. The lipodystrophy protein seipin is a key player in LD biogenesis and ER-LD contact site maintenance. Recent structural and in silico studies have started to shed light on the molecular function of seipin as a LD nucleator in early LD biogenesis, whilst new cell biological work implies a role for seipin in ER-mitochondria contact sites and calcium metabolism. In this minireview, I discuss recent insights into the molecular function of seipin.

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A unifying mechanism for seipin‐mediated lipid droplet formation

Klug,

Ferreira,

Carvalho

2024

FEBS Letters

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Lipid droplets (LDs) are dynamic organelles essential for cellular lipid homeostasis. Assembly of LDs occurs in the endoplasmic reticulum (ER), and the conserved ER membrane protein seipin emerged as a key player in this process. Here, we review recent advances provided by structural, biochemical, and in silico analysis that revealed mechanistic insights into the molecular role of the seipin complexes and led to an updated model for LD biogenesis. We further discuss how other ER components cooperate with seipin during LD biogenesis. Understanding the molecular mechanisms underlying seipin‐mediated LD assembly is important to uncover the fundamental aspects of lipid homeostasis and organelle biogenesis and to provide hints on the pathogenesis of lipid storage disorders.

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CG32803 is the fly homolog of LDAF1 and influences lipid storage in vivo

Cited by 6 publications

References 43 publications

A metabolically controlled contact site between lipid droplets and vacuoles

A metabolically controlled contact site between lipid droplets and vacuoles

Seipin—still a mysterious protein?

A unifying mechanism for seipin‐mediated lipid droplet formation

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