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Review
. 2019 Jun 11:5:14.
doi: 10.1186/s41016-019-0162-y. eCollection 2019.

ACSS2-related autophagy has a dual impact on memory

Hao Zhang  1 , Zujian Xiong  1 , Qin He  1 , Fan Fan  1
Affiliations
Review

ACSS2-related autophagy has a dual impact on memory

Hao Zhang et al. Chin Neurosurg J. .

Abstract

Autophagy is an intracellular degenerative pathway which is responsible for neuronal survival. Under the condition of nutrient deprivation, autophagy can lead to dysfunction in memory consolidation. AMPK/mTOR pathway is currently the most studied autophagy mechanism, while recently researchers have proved ACSS2 can also affect autophagy. ACSS2 is phosphorylated at Ser659 by AMPK and then forms a translocation complex with Importin α5 to translocate into the nucleus. This process interacts with TFEB, resulting in upregulated expression of lysosomal and autophagosomal genes. These upregulations inhibit synaptic plasticity and hence memory functions. On the other hand, ACSS2 is also recognized as a regulator of histone acetylation. After recruiting CBP/p300 and activating CBP's HAT activity in the nucleus, ACSS2 maintains the level of localized histone acetylation by recapturing acetate from histone deacetylation to reform acetyl-CoA, providing substrates for HAT. The increase of histone acetylation locally enhanced immediate early gene transcription, including Egr2, Fos, Nr2f2, Sgk1, and Arc, to benefit neuronal plasticity and memory in many ways.

Keywords: ACSS2; Histone acetylation; Memory; TFEB.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Glucose deprivation resulted in AMPK-phosphorylation-dependent formation of an ACSS2 and TFEB complex in the promoter regions of lysosomal and autophagy genes, where ACSS2 incorporated acetate from the turnover of histone acetylation into acetyl-CoA for histone H3 acetylation, gene expression, and enhanced lysosomal biogenesis and autophagy
Fig. 2
Fig. 2
BDNF via TrkB and PI3K/Akt pathway in the hippocampus suppresses autophagic flux and autophagosomes. mTORC1 phosphorylates Atg13 and inhibits Atg1, which is a necessary condition for suppressing autophagy
Fig. 3
Fig. 3
CBP has histone acetyltransferase (HAT) activity in which the metabolite acetyl-CoA is required for histone acetylation. ACSS2 maintains the level of localized histone acetylation by recapturing acetate from histone deacetylation to reform acetyl-CoA, providing substrates for HAT
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