accepted manuscript

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been observed [207]. Curiously, an increase of extracellular striatal dopamine occured
in some parkin knockout mice (Δexon3; [208, 209]. Gautier et al. reported a subtle
increase in larger, but ultrastructurally normal mitochondria, a mild reduction in
mitochondrial respiration in the striatum of young (3-4 months) and in the cortex of
aged (22-24 months) PINK1 knockout mice, which, however, did not lead to reduced
ATP levels [122]. Even in aged PINK1 knockout mice levels of oxidative stress
markers were unchanged. In a different PINK1 knockout mouse line Gispert et al.
observed progressive reduction of body weight and spontaneous locomotor activity in
the absence of nigrostriatal degeneration [124]. Whether locomotor deficits in these
mice were L-dopa responsive has not been reported. Furthermore, import of pre-
proteins in liver mitochondria from these PINK1-deficient mice was impaired in an
age-dependent manner [124]. This is an interesting observation which raises the
question whether PINK1 per se has an effect on mitochondrial import or whether the
defective import observed in PINK1-deficient mice is a consequence of the reduced
mitochondrial membrane potential.
In contrast to parkin and PINK1 knockout mice, Drosophila null mutants
show a striking and remarkably similar phenotype, characterized by reduced life span,
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male sterility, and locomotor defects due to apoptotic flight muscle degeneration
[210-214]. The earliest manifestation of muscle degeneration and defective
spermatogenesis was mitochondrial pathology, exemplified by swollen mitochondria
and disintegrated cristae. [210]. Strikingly, parkin could compensate for the PINK1
loss-of-function phenotype, but not vice versa, implying that PINK1 and parkin
function in a common genetic pathway with parkin acting downstream of PINK1
[211-213]. Subsequent studies in Drosophila suggested that parkin and PINK1 may
have a possible role in modulating mitochondrial morphology and dynamics [215-
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