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

Cell death-Inducing DNA Fragmentation Factor Alpha (DFFA)-like Effector (CIDE) proteins have emerged as lipid droplet-associated proteins that regulate fat metabolism. There are three members in the CIDE protein family—CIDEA, CIDEB, and CIDEC (also known as fat-specific protein 27 (FSP27)). CIDEA and FSP27 are primarily expressed in adipose tissue, while CIDEB is expressed in the liver. Originally, based upon their homology with DNA fragmentation factors, these proteins were identified as apoptotic proteins. However, recent studies have changed the perception of these proteins, redefining them as regulators of lipid droplet dynamics and fat metabolism, which contribute to a healthy metabolic phenotype in humans. Despite various studies in humans and gene-targeting studies in mice, the physiological roles of CIDE proteins remains elusive. This review will summarize the known physiological role and metabolic pathways regulated by the CIDE proteins in human health and disease.

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Cell death-inducing DNA fragmentation factor A-like effector A and fat-specific protein 27β coordinately control lipid droplet size in brown adipocytes

Journal of Biological Chemistry ◽

10.1074/jbc.m116.768820 ◽

2017 ◽

Vol 292 (26) ◽

pp. 10824-10834 ◽

Cited By ~ 8

Author(s):

Yuki Nishimoto ◽

Shinsuke Nakajima ◽

Sanshiro Tateya ◽

Masayuki Saito ◽

Wataru Ogawa ◽

...

Keyword(s):

Cell Death ◽

Dna Fragmentation ◽

Droplet Size ◽

Lipid Droplet ◽

Specific Protein ◽

Brown Adipocytes ◽

Lipid Droplet Size

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1705949114 ◽

2017 ◽

Vol 114 (28) ◽

pp. 7361-7366 ◽

Cited By ~ 11

Author(s):

Jae Young Choi ◽

Qi Qiao ◽

Se-Hoon Hong ◽

Chang Min Kim ◽

Jae-Hee Jeong ◽

...

Keyword(s):

Cell Death ◽

Dna Fragmentation ◽

Lipid Droplet ◽

Family Members ◽

Higher Order ◽

Lipid Homeostasis ◽

Biological Processes ◽

Helical Structures

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.

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