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Updated: Jun 7, 2026

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Which CIDE are you on? Apoptosis and energy metabolism
Tomo Yonezawa1, Riho Kurata, Minoru Kimura
1Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Bohseidai, Ishehara, Kanagawa 259-1193, Japan. yonet2301@yahoo.co.jp
Abstract:
Around 1998, cell death-inducing DNA fragmentation factor-alpha (DFFA)-like effector (CIDE) proteins including CIDEA, CIDEB and CIDEC/fat specific protein 27 (Fsp27) were first identified by their sequence homology with the N-terminal domain of the DNA fragmentation factor (DFF). Indeed, in vitro analysis revealed that all three CIDE proteins are involved in apoptosis. However, recent gene-targeting studies have provided novel insights into the physiological function of CIDE proteins. Mice deficient in each CIDE protein exhibit lean phenotypes, a reduction of lipid droplet size in white adipose tissue and increased metabolic rate. Thus, all CIDE proteins play an important role in energy metabolism and lipid droplet formation. More recently, a glycoproteomics approach has shown that post-translational regulation of CIDE proteins via glycosylation modulates transforming growth factor (TGF)-beta 1-dependent apoptosis. Another recent study using mouse embryonic fibroblasts derived from CIDEA-deficient mice revealed that 5'AMP-activated protein kinase (AMPK) activity is regulated by CIDEA-mediated ubiquitin-dependent proteasomal degradation via a protein interaction with the AMPK beta subunit. Even after a decade of study, the physiological roles of CIDE proteins have still not been completely elucidated. This review aims to shed light on the novel functions of CIDE proteins and their physiological roles.
Insights
Cell death-inducing DNA fragmentation factor-alpha (CIDE) proteins regulate energy metabolism and lipid droplet formation. Novel research reveals their roles in apoptosis and AMPK activity, expanding our understanding of CIDE protein functions.
Area of Science:
- Molecular Biology
- Cell Biology
- Metabolic Research
Background:
- Cell death-inducing DNA fragmentation factor-alpha (CIDE) proteins (CIDEA, CIDEB, CIDEC/Fsp27) were identified in 1998.
- Initial studies indicated their involvement in apoptosis.
- Recent research suggests broader physiological roles beyond apoptosis.
Purpose of the Study:
- To review and elucidate novel functions of CIDE proteins.
- To explore the physiological roles of CIDE proteins in energy metabolism and lipid droplet formation.
- To highlight recent findings on post-translational modifications and protein interactions.
Main Methods:
- Gene-targeting studies in mice.
- Glycoproteomics analysis.
- Studies using mouse embryonic fibroblasts.
Main Results:
- Mice deficient in CIDE proteins show lean phenotypes, reduced lipid droplet size, and increased metabolic rate.
- Glycosylation of CIDE proteins influences TGF-beta 1-dependent apoptosis.
- CIDEA regulates AMPK activity through ubiquitin-dependent proteasomal degradation.
Conclusions:
- CIDE proteins are crucial regulators of energy metabolism and lipid droplet formation.
- Post-translational modifications and protein interactions significantly impact CIDE protein function.
- Further research is needed to fully elucidate the complex physiological roles of CIDE proteins.
Related Concept Videos
Caspases
Cellular Injury V: Apoptosis and Autophagy
Apoptosis
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
Introduction to Metabolism

