A neuroprotective role of Ufmylation through Atg9 in the aging brain of Drosophila.
Huifang LiZhenghong YuZikang NiuYun ChengZhenhao WeiYafei CaiFei MaLanxin HuJiejie ZhuWei ZhangPublished in: Cellular and molecular life sciences : CMLS (2023)
Ufmylation is a recently identified small ubiquitin-like modification, whose biological function and relevant cellular targets are poorly understood. Here we present evidence of a neuroprotective role for Ufmylation involving Autophagy-related gene 9 (Atg9) during Drosophila aging. The Ufm1 system ensures the health of aged neurons via Atg9 by coordinating autophagy and mTORC1, and maintaining mitochondrial homeostasis and JNK (c-Jun N-terminal kinase) activity. Neuron-specific expression of Atg9 suppresses the age-associated movement defect and lethality caused by loss of Ufmylation. Furthermore, Atg9 is identified as a conserved target of Ufm1 conjugation mediated by Ddrgk1, a critical regulator of Ufmylation. Mammalian Ddrgk1 was shown to be indispensable for the stability of endogenous Atg9A protein in mouse embryonic fibroblast (MEF) cells. Taken together, our findings might have important implications for neurodegenerative diseases in mammals.
Keyphrases
- signaling pathway
- cell death
- induced apoptosis
- endoplasmic reticulum stress
- oxidative stress
- healthcare
- cerebral ischemia
- cell cycle arrest
- public health
- transcription factor
- genome wide
- health information
- white matter
- brain injury
- pi k akt
- climate change
- multiple sclerosis
- risk assessment
- long non coding rna
- small molecule
- social media
- subarachnoid hemorrhage
- cell proliferation
- spinal cord
- dna methylation
- genome wide identification