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EI24 tethers endoplasmic reticulum and mitochondria to regulate autophagy flux

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A Correction to this article was published on 21 November 2019

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Abstract

Etoposide-induced protein 2.4 (EI24), located on the endoplasmic reticulum (ER) membrane, has been proposed to be an essential autophagy protein. Specific ablation of EI24 in neuronal and liver tissues causes deficiency of autophagy flux. However, the molecular mechanism of the EI24-mediated autophagy process is still poorly understood. Like neurons and hepatic cells, pancreatic β cells are also secretory cells. Pancreatic β cells contain large amounts of ER and continuously synthesize and secrete insulin to maintain blood glucose homeostasis. Yet, the effect of EI24 on autophagy of pancreatic β cells has not been reported. Here, we show that the autophagy process is inhibited in EI24-deficient primary pancreatic β cells. Further mechanistic studies demonstrate that EI24 is enriched at the ER–mitochondria interface and that the C-terminal domain of EI24 is important for the integrity of the mitochondria-associated membrane (MAM) and autophagy flux. Overexpression of EI24, but not the EI24-ΔC mutant, can rescue MAM integrity and decrease the aggregation of p62 and LC3II in the EI24-deficient group. By mass spectrometry-based proteomics following immunoprecipitation, EI24 was found to interact with voltage-dependent anion channel 1 (VDAC1), inositol 1,4,5-trisphosphate receptor (IP3R), and the outer mitochondrial membrane chaperone GRP75. Knockout of EI24 impairs the interaction of IP3R with VDAC1, indicating that these proteins may form a quaternary complex to regulate MAM integrity and the autophagy process.

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  • 21 November 2019

    In the published article, few errors were noticed and this has been corrected with this erratum publication.

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Acknowledgements

This project was supported by the National Key R&D Program of China (2017YFA0505300 and 2016YFA0501500), the National Natural Science Foundation of China (31421002, 21778069 and 31401174), Project of the Chinese Academy of Sciences (XDB08030203) and Project of Chinese Academy of Sciences-Peking University Leading Cooperation Team.

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  1. Lin Yuan and Qi Liu contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Lin Yuan, Qi Liu, Zhe Wang & Pingyong Xu

  2. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100101, China

    Qi Liu, Zhe Wang & Pingyong Xu

  3. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Junjie Hou & Pingyong Xu

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  1. Lin Yuan
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  2. Qi Liu
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  3. Zhe Wang
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  4. Junjie Hou
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Correspondence to Pingyong Xu.

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Yuan, L., Liu, Q., Wang, Z. et al. EI24 tethers endoplasmic reticulum and mitochondria to regulate autophagy flux. Cell. Mol. Life Sci. 77, 1591–1606 (2020). https://doi.org/10.1007/s00018-019-03236-9

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  • DOI: https://doi.org/10.1007/s00018-019-03236-9

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