The p53-induced Gene Ei24 Is an Essential Component of the Basal Autophagy Pathway

• Published in: The Journal of biological chemistry Vol. 287; no. 50; pp. 42053 - 42063
• Main Authors: Zhao, Yan G., Zhao, Hongyu, Miao, Lin, Wang, Li, Sun, Fei, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.12.2012; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; autophagosome; Autophagy; Autophagy - physiology; Axons - metabolism; C. elegans; Hepatocyte; Hepatocytes - metabolism; Heredodegenerative Disorders, Nervous System - genetics; Heredodegenerative Disorders, Nervous System - metabolism; Mice; Mice, Transgenic; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neurodegeneration; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oligodendrocytes; Oligodendroglia - metabolism; Organ Specificity - genetics; p53; Signal Transduction; Transcription Factor TFIIH; Transcription Factors - immunology; Transcription Factors - metabolism; C. elegans; Hepatocyte; Neurodegeneration; Oligodendrocytes; Autophagy; autophagosome; p53
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.M112.415968

Ei24 is a DNA damage response gene involved in growth suppression and apoptosis. The physiological function of Ei24, however, is poorly understood. Here we generated conditional knock-out mice of Ei24 and demonstrated that EI24 is an essential component of the basal autophagy pathway. Mice with neural-specific Ei24 deficiency develop age-dependent neurological abnormalities caused by massive axon degeneration and extensive neuron loss in brain and spinal cord. Notably, ablation of Ei24 leads to vacuolated oligodendroglial cells and demyelination of axons. Liver-specific depletion of Ei24 causes severe hepatomegaly with hepatocyte hypertrophy. Ei24 deficiency impairs autophagic flux, leading to accumulation of LC3, p62 aggregates, and ubiquitin-positive inclusions. Our study indicates that Ei24 is an essential autophagy gene and plays an important role in clearance of aggregate-prone proteins in neurons and hepatocytes. Background: The function of the p53-induced gene Ei24 in the autophagy pathway remains largely unknown. Results:Ei24 deficiency impairs autophagic flux. Mice deficient in Ei24 show massive neuron degeneration and severe liver injury. Conclusion:Ei24 functions in basal autophagy in clearance of aggregate-prone proteins in neurons and hepatocytes. Significance: We revealed that EI24 is an essential component of the basal autophagy pathway.