Редактирование: ATG9A

Autophagy-related protein 9A (APG9-like 1) (mATG9) [APG9L1]

==Publications==

{{medline-entry
|title=[[SIRT1]] protects cochlear hair cell and delays age-related hearing loss via autophagy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31170533
|abstract=Age-related hearing loss (AHL) is typically caused by the irreversible death of hair cells (HCs). Autophagy is a constitutive pathway to strengthen cell survival under normal or stress condition. Our previous work suggested that impaired autophagy played an important role in the development of AHL in C57BL/6 mice, although the underlying mechanism of autophagy in AHL still needs to be investigated. [[SIRT1]] as an important regulator involves in AHL and is also a regulator of autophagy. Thus, we hypothesized that the modulation between [[SIRT1]] and autophagy contribute to HC death and the progressive hearing dysfunction in aging. In the auditory cell line HEI-OC1, [[SIRT1]] modulated autophagosome induction because of [[SIRT1]] deacetylating a core autophagy protein [[ATG9A]]. The deacetylation of [[ATG9A]] not only affects the autophagosome membrane formation but also acts as a sensor of endoplasmic reticulum (ER) stress inducing autophagy. Moreover, the silencing of [[SIRT1]] facilitated cell death via autophagy inhibition, whereas [[SIRT1]] and autophagy activation reversed the [[SIRT1]] inhibition media cell death. Notably, resveratrol, the first natural agonist of [[SIRT1]], altered the organ of Corti autophagy impairment of the 12-month-old C57BL/6 mice and delayed AHL. The activation of [[SIRT1]] modulates the deacetylation status of [[ATG9A]], which acts as a sensor of ER stress, providing a novel perspective in elucidating the link between ER stress and autophagy in aging. Because [[SIRT1]] activation restores autophagy with reduced HC death and hearing loss, it could be used as a strategy to delay AHL.
|mesh-terms=* Acetylation
* Aging
* Animals
* Autophagy
* Autophagy-Related Proteins
* Endoplasmic Reticulum Stress
* Hair Cells, Auditory
* Hearing Loss, Sensorineural
* Membrane Proteins
* Mice, Inbred C57BL
* Sirtuin 1
* Vesicular Transport Proteins
|keywords=* Age-related hearing loss
* Autophagy
* Cell death
* Resveratrol
* SIRT1
|full-text-url=https://sci-hub.do/10.1016/j.neurobiolaging.2019.04.003
}}
{{medline-entry
|title=Activation of miR-34a impairs autophagic flux and promotes cochlear cell death via repressing [[ATG9A]]: implications for age-related hearing loss.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28981097
|abstract=Age-related hearing loss is a major unresolved public health problem. We have previously elucidated that the activation of cochlear miR-34a is correlated with age-related hearing loss in C57BL/6 mice. A growing body of evidence points that aberrant autophagy promotes cell death during the development of multiple age-related diseases. The aim of this study was to investigate the role of miR-34a-involved disorder of autophagy in the pathogenesis of age-related hearing loss. Our results showed that miR-34a expression was markedly upregulated in the aging cochlea accompanied with impairment of autophagic flux. In the inner ear HEI-OC1 cell line, miR-34a overexpression resulted in an accumulation of phagophores and impaired autophagosome-lysosome fusion, and led to cell death subsequently. Notably, autophagy-related protein 9A ([[ATG9A]]), an autophagy protein, was significantly decreased after miR-34a overexpression. Knockdown of [[ATG9A]] inhibited autophagy flux, which is similar to the effects of miR-34a overexpression. Moreover, ursodeoxycholic acid significantly rescued miR-34a-induced HEI-OC1 cell death by restoring autophagy activity. Collectively, these findings increase our understanding of the biological effects of miR-34a in the development of age-related hearing loss and highlight miR-34a as a promising therapeutic target for its treatment.
|mesh-terms=* Aging
* Animals
* Autophagy
* Autophagy-Related Proteins
* Cell Line
* Cochlea
* Disease Models, Animal
* Gene Expression Regulation
* Hearing Loss
* Humans
* Membrane Proteins
* Mice
* MicroRNAs
* Vesicular Transport Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680584
}}