Growing evidence supports an active role for dysregulated macroautophagy 
(autophagic stress) in neuronal cell death and neurodegeneration. Alterations in 
mitochondrial function and dynamics are also strongly implicated in 
neurodegenerative diseases. Interestingly, whereas the core autophagy machinery 
is evolutionarily conserved and shared among constitutive and induced or 
selective autophagy, recent studies implicate distinct mechanisms regulating 
mitochondrial autophagy (mitophagy) in response to general autophagic stimuli. 
Little is known about pathways regulating selective, damage-induced mitophagy. 
We found that the parkinsonian neurotoxin MPP(+) induces autophagy and 
mitochondrial degradation that is inhibited by siRNA knockdown of autophagy 
proteins Atg5, Atg7 and Atg8, but occurs independently of Beclin 1, a component 
of the class III (PIK3C3/Vps34) phosphoinositide 3-kinase (PI3K) complex. 
Instead, MPP(+)-induced mitophagy is dependent upon MAPK signaling. 
Interestingly, all treatments that inhibited autophagy also conferred protection 
from MPP(+)-induced cell death. A prior human tissue study further supports a 
role for ERK/MAPK-regulated autophagy in Parkinson's and Lewy body diseases. As 
competition for limiting amounts of Beclin 1 may serve to prevent harmful 
overactivation of autophagy, understanding mechanisms that bypass or complement 
a requirement for PI3K-Beclin 1 activity could lead to strategies to modulate 
autophagic stress in injured or degenerating neurons.