We further discovered that PINK1 can phosphorylate and activate PKA, a master regulator of synaptic function and many other cellular functions related to extracellular and calcium signals. We propose that functioning mitochondria release processed and active PINK1, which acts as a signal of mitochondrial health, cooperating with VCP to promote dendritic extension, branching or maintenance. In contrast, depolarized mitochondria are unable to import, process and release PINK1, resulting in recruitment of Parkin and activation of one of the pathways leading to mitochondrial disposal through mitophagy.
Interestingly, mutations in VCP also cause neurodegeneration (frontotemporal dementia) as well as muscle and bone diseases. The convergence of two genes linked to different neurodegenerative diseases suggests that strategies to enhance this pathway may lead to new therapeutic directions.
Read more in eNeuro: https://www.eneuro.org/content/5/6/ENEURO.0466-18.2018
Read the F1000 recommendation at: https://f1000.com/prime/734664398
See also: https://chulab.weebly.com/news/our-fifth-faculty-of-1000-recommended-article