Cytosolic PINK1 escapes from mitochondria to promote dendritic outgrowth

Abstract

Dagda et al. showed in this issue that cytosolic PINK1 released from the mitochondrion promotes dendritic outgrowth. This neurite-promoting activity of PINK1 is associated with the kinase activities of protein kinase A and is impaired by a pathogenic mutation in PINK1. The study by Dagda et al. has unravelled a novel mechanism underlying neurodegeneration caused by PINK1 mutation.

Figure. PINK1 promotes synaptic activity

Under normal conditions, PINK1 is present both in the mitochondria and the cytosol. Full-length PINK1 is cleaved by presenilin-associated rhomboid-like protein (PARL) and released to the cytosol. The results by Dagda et al. (2013) indicate that it is cytosolic rather than mitochondrial PINK1 that promotes anterograde mitochondrial transport in dendrites, leading to increased dendritic mitochondrial density and dendritic outgrowth. Under pathological conditions, PINK1 remains uncleaved and neuronal differentiation is blocked. At the axonal terminals, a loss of PINK1 function has been reported by other studies to impair pre-synaptic dopamine (DA) release. It is possible that PINK1 maintains presynaptic release of neurotransmitters by maintaining proper mitochondrial function to meet much needed energy demand by synaptic terminals for various homeostasis functions. Together, PINK1 appears to play an important role in synaptic function at both pre- and post-synaptic levels.