Selective mitochondrial degradation through autophagy (mitophagy) has emerged as an important homeostatic mechanism in a variety of organisms and contexts. Complete clearance of mitochondria can be observed during normal maturation of certain mammalian cell types, and during certain forms of neuronal cell death. In recent years, autophagy dysregulation has been implicated in toxin-injured dopaminergic neurons as well as in major genetic models of Parkinson's disease (PD), including α-synuclein, leucine-rich repeat kinase 2 (LRRK2), parkin, PTEN-induced kinase 1 (PINK1), and DJ-1. Indeed, PINK1-parkin interactions may form the basis of a mechanism by which dissipation of the inner mitochondrial membrane potential can trigger selective mitochondrial targeting for autophagy. Multiple signals are likely to exist, however, depending upon the trigger for mitophagy. Similarly, the regulation of basal or injury-induced autophagy does not always follow canonical pathways described for nutrient deprivation. Implications of this regulatory diversity are discussed in the context of neuronal function and survival. Further studies are needed to address whether alterations in autophagy regulation play a directly injurious role in PD pathogenesis, or if the observed changes reflect impaired, appropriate, or excessive autophagic responses to other forms of cellular injury. 1. Introduction Macroautophagy represents an evolutionarily conserved response to nutrient stresses, which also plays an increasingly recognized role in basal cellular maintenance and in cellular responses to injury. The important role of macroautophagy in brain development and quality control was highlighted by observations that mice engineered for deficiency in key autophagy genes exhibit spontaneous neurodegeneration with ubiquitinated protein aggregates [1, 2]. Macroautophagy (hereafter, autophagy unless otherwise specified) is also implicated in mitochondrial quality control, as altered mitochondria accumulate under basal conditions of autolysosomal dysfunction [3–6], and mitophagy is further induced in cells exhibiting damaged mitochondria [7, 8]. Mitochondrial autophagy induced in response to mitochondrial damage or neuronal injury may play either prosurvival [7, 9] or prodeath roles [10, 11]. As mechanisms underlying different models of injury-induced autophagy and mitophagy are discovered, the concept of distinct regulatory inputs to a core autophagy pathway has emerged. In sympathetic neurons, it was noted that the phosphoinositide 3-kinase inhibitor 3-methyladenine (3-MA) delayed apoptosis
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