The p53-induced gene Ei24 is an essential component of the basal autophagy pathway.
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.
State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, P.R. China.
Yan G
YG
Zhao
Hongyu
H
Zhao
Lin
L
Miao
Li
L
Wang
Fei
F
Sun
Hong
H
Zhang
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C526185:EI24 protein, mouse; C490981:Gtf2h1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051758:Transcription Factor TFIIH