Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy

Qian Yang, Hua She, Marla Gearing, Emanuela Colla, Michael Lee, John J. Shacka, Zixu Mao

Research output: Contribution to journalArticlepeer-review

273 Scopus citations


Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of a-synuclein transgenic mice and patients with Parkinson's disease. Wild-type α-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)124-127
Number of pages4
Issue number5910
StatePublished - Jan 2 2009
Externally publishedYes


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