CIDE Proteins and Lipid Metabolism

Xu, Li; Zhou, Linkang; Li, Peng

doi:10.1161/atvbaha.111.241489

Cited by 144 publications

(118 citation statements)

References 73 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…A distinct LD fusion process emerged from the study of CIDE proteins, which are required for the formation of supersized LDs in adipocytes [33]. Both CIDEA and CIDEC catalyse a slow fusion mechanism in which a donor LD transfers its content to a larger LD in a process driven by their internal pressure gradient [34].…”

Section: Ld-ld Fusionmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

View full text Add to dashboard Cite

Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules.Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving. The dynamic expression of LD-associated proteins is vital for controlling LD biology and is most apparent during adipocyte differentiation. Recent findings on the molecular mechanisms of lipid droplet enlargement reveal the importance of distinct functional groups of proteins and phospholipids.Highlights (max 5 points 85 characters each) Lipid droplet fusion involves major changes in the LD membrane components.Phosphatidic Acid is a key regulator of LD dynamics.Adipocyte differentiation invokes profound regulation of lipid droplet proteins.Transitions between white and BRITE adipocytes require lipid droplet remodelling.

show abstract

Section: Ld-ld Fusionmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

View full text Add to dashboard Cite

show abstract

“…The sizes of LDs reflect different biological processes. Several models projecting the growth of LDs have been proposed, including targeted lipid delivery from the endoplasmic reticulum to LDs mediated by fat storage-inducing transmembrane proteins 1 and 2 (FITM1/2) (10), local lipid synthesis on LDs mediated by CTP:phosphocholine cytidylyltransferase and diacylglycerol acyltransferase 2 (DGAT2) (11,12), and the fusion of smaller LDs into larger LDs mediated by CIDEs in adipocytes (13).…”

mentioning

confidence: 99%

Differential Roles of Cell Death-inducing DNA Fragmentation Factor-α-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

“…Besides the nucleases, CIDEA, CIDEB, and FSP27 also display self-complementary electrostatic surfaces, suggesting that these proteins also may form higher-order structures to promote lipid droplet exchange and fusion (17). Previous studies have noted FSP27 homodimers in their crystal structures (22,23).…”

Section: A B Cmentioning

confidence: 97%

“…S1A), and their disruption can result in obesity, diabetes, liver steatosis, and cardiovascular diseases. CIDEA, CIDEB, and FSP27 are known to localize at lipid droplet contact sites, promoting lipid transfer and lipid droplet fusion in adipocytes and hepatocytes (17,18).CIDE domains possess an α/β roll structure with two α-helices and five β-strands as determined by NMR spectroscopy (19). NMR structures of CIDE domain complexes of DFF40-DFF45 and CAD-ICAD exhibit asymmetric heterodimers with charge complementarity (20, 21), and the crystal structure of the CIDE domain of FSP27 shows the molecular basis of homodimerization (22,23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

CIDE domains form functionally important higher-order assemblies for DNA fragmentation

Choi

Qiao

Hong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Cell death-inducing DFF45-like effector (CIDE) domains, initially identified in apoptotic nucleases, form a family with diverse functions ranging from cell death to lipid homeostasis. Here we show that the CIDE domains of Drosophila and human apoptotic nucleases Drep2, Drep4, and DFF40 all form head-to-tail helical filaments. Opposing positively and negatively charged interfaces mediate the helical structures, and mutations on these surfaces abolish nuclease activation for apoptotic DNA fragmentation. Conserved filamentous structures are observed in CIDE family members involved in lipid homeostasis, and mutations on the charged interfaces compromise lipid droplet fusion, suggesting that CIDE domains represent a scaffold for higher-order assembly in DNA fragmentation and other biological processes such as lipid homeostasis.CIDE family | higher-order structure | DNA fragmentation | apoptosis | lipid homeostasis A hallmark of apoptosis is the fragmentation of cellular genomic DNA into a laddered pattern composed of multiples of 180-to 200-bp pieces, which correspond to the DNA length in a nucleosome. Two decades ago, the enzyme responsible for regulated DNA fragmentation was identified from human HeLa cells as a heterodimeric complex of the nuclease DNA fragmentation factor (DFF) of 40 kDa (DFF40), and the inhibitor of 45 kDa (DFF45) (1). Independently, a heterodimeric complex of caspase-activated DNase (CAD) and its inhibitor (ICAD) was identified from mouse lymphoma cells (2, 3). DFF45 and ICAD chaperone the folding of DFF40 and CAD, respectively, and also trap them in inactive states through complex formation. On induction of apoptosis, DFF45 and ICAD are cleaved by activated caspases to release DFF40 and CAD for nuclear translocation and digestion of genomic DNA through large-scale chromatin fragmentation and internucleosomal DNA cleavage (1, 4).DNA fragmentation is the basis for the classical apoptotic TUNEL assay that detects DNA double-strand breaks (5). Because apoptotic cells display "eat-me" signals and are phagocytosed, DNA fragmentation has been proposed as a mechanism for avoiding the transformation of recipient cells by the activated oncogenes or viral genes and reduce the autoimmune response from the strong autoantigenic DNA (6). Clinically, sperm DNA fragmentation is used as a correlative to male infertility (7), and circulating fragmented cellfree DNA is detected as a disease biomarker (8).Human DFF40 and DFF45 and mouse CAD and ICAD contain a conserved N-terminal region known as the cell death-inducing DFF45-like effector (CIDE) domain (9) (Fig. S1A). In Drosophila, four DFF-related proteins (Drep1-4) are critical for apoptotic DNA fragmentation (10-12) (Fig. S1A), and Drep2 also acts as a unique synaptic protein important in learning and behavioral adaptation (13). Biochemical characterization of CIDE-CIDE interactions from Drep1 to Drep4 has revealed that the Drep2 and Drep4 nucleases interact with and are inhibited by . In addition to DNA fragmentation, the CIDE domain-containing proteins CIDEA...

show abstract

CIDE Proteins and Lipid Metabolism

Cited by 144 publications

References 73 publications

Lipid droplet growth: regulation of a dynamic organelle

Lipid droplet growth: regulation of a dynamic organelle

Differential Roles of Cell Death-inducing DNA Fragmentation Factor-α-like Effector (CIDE) Proteins in Promoting Lipid Droplet Fusion and Growth in Subpopulations of Hepatocytes

CIDE domains form functionally important higher-order assemblies for DNA fragmentation

Contact Info

Product

Resources

About