Seipin regulates lipid homeostasis by ensuring calcium‐dependent mitochondrial metabolism

Ding, Lin‐Fen; Yang, Xiao; Tian, He; Liang, Jingjing; Zhang, Fengxia; Wang, Guodong; Wang, Yingchun; Ding, Mei; Shui, Guanghou; Huang, Xun

doi:10.15252/embj.201797572

Cited by 66 publications

(61 citation statements)

References 67 publications

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“…Seipin mutant flies display fat body-autonomous reductions in LD size and organismal TAG levels (Tian et al 2011). Notably, this deficit in TAG storage has been linked to impaired activity of the ER Ca 2+ pump SERCA (Bi et al 2014) and subsequent mitochondrial dysfunction, which leads to reduced lipogenesis (Ding et al 2018). The Seipin mutant also represents a striking example of ectopic fat accumulation in salivary glands, which is unrelated to the function of Seipin in the fat body.…”

Section: Tag Storage: Formation Of Ldsmentioning

confidence: 99%

Triacylglycerol Metabolism in Drosophila melanogaster

2018

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Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the Drosophila model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism in vivo. Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and de novo lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.

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Section: Tag Storage: Formation Of Ldsmentioning

confidence: 99%

Triacylglycerol Metabolism in Drosophila melanogaster

2018

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“…Huntington's disease cells, including primary striatal neurons and glia in Huntington's disease mice, have dramatically increased LDs (Martinez-Vicente, Talloczy et al, 2010). Several hereditary spastic paraplegia (HSP) proteins affect LD dynamics, such as Spartin, spastin, atlastin-1, seipin and REEP1 (Ding, Yang et al, 2018, Eastman, Yassaee et al, 2009, Ebihara, Ebihara et al, 2015, Klemm, Norton et al, 2013, Papadopoulos, Orso et al, 2015, Renvoise, Malone et al, 2016. Despite the apparent association between LD and neuronal diseases, the causal link between neuronal LD dynamics and neuronal disorders remains largely elusive.…”

Section: Introductionmentioning

confidence: 99%

Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration

Yang

Liang

Lam

et al. 2020

Preprint

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Highlights:1. Neuronal lipolysis prevents LD accumulation in neurons.2. Defective neuronal lipolysis leads to touch sensation defect.3. Blocking neuronal lipolysis alleviates neurodegeneration. 4. Neuronal lipolysis and de novo PUFA biosynthesis have a synergistic effect in neurodegeneration. The incorporation of PUFAs into phospholipids promotes neurodegeneration. AbstractLipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl-1 and lid-1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects, synergistically with decreased lipolysis.Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in regulating neural functions and neurodegeneration cell-autonomously.

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“…Besides, calcium is one of the most well-studied ions in mitochondria. An increase in mitochondrial calcium levels can activate ATP production, brown fat thermogenesis, and browning of white fat by altering the activity of calcium-sensitive proteins such as NCLX and SERCA2b (Williams et al, 2015;Ding et al, 2018;Pathak and Trebak, 2020). Zinc may also play important roles in mitochondrial functionality by serving as ion center for zinc finger proteins.…”

Section: Discussionmentioning

confidence: 99%

Transferrin Receptor Functionally Marks Thermogenic Adipocytes

Qiu

Zhang

Wang

et al. 2020

Front. Cell Dev. Biol.

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Background: Thermogenic adipocytes, including beige and brown adipocytes, are critical for thermogenesis and energy homeostasis. Identification of functional cell surface markers of thermogenic adipocytes is of significance for potential application in biological and clinical practices. Methods: With a combination of RNA-sequencing of in vivo and in vitro models, we identified transferrin receptor (Tfr1), a receptor specialized for cellular iron uptake, as a previously unappreciated cell surface molecule for thermogenic adipocytes compared to white adipocytes. The alternation of Tfr1 levels under physiological and pathological stimuli was assessed, and the mitochondria functionality, browning capacity, and iron metabolism of mature adipocytes were examined with Tfr1 knockdown. Results: Tfr1 was expressed predominantly in thermogenic adipocytes versus white adipocyte, and its expression levels were tightly correlated with the activation or inhibition status of thermogenic adipocytes under external stimuli. Besides, Tfr1 gene deficiency in thermogenic adipocytes led to reduced thermogenic gene programs and mitochondrial integrity. Conclusion: Tfr1 functionally marks thermogenic adipocytes and could serve as a potential thermogenic adipocyte surface marker.

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Seipin regulates lipid homeostasis by ensuring calcium‐dependent mitochondrial metabolism

Cited by 66 publications

References 67 publications

Triacylglycerol Metabolism in Drosophila melanogaster

Triacylglycerol Metabolism in Drosophila melanogaster

Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration

Transferrin Receptor Functionally Marks Thermogenic Adipocytes

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