PINK1 Deficiency Figure 7. Abnormal lysosomal morphology in PINK1 kd neurons. A) TEM images of vesicular aggregates within surviving aged human neurons lacking PINK1 at dd47. A control neuron is shown in panel A. Panels b-d show aggregates in PINK1 kd neurons, panel c is an aggregate enlarged from b. Scale bars; a, b; 20 mM, d; 2 mM. B) Immunofluorescence images of aged (dd47) control human neurons (panels a-c) and PINK1 kd neurons (d–f) showing lysosomal morphology (red staining; panels b and e). Nuclei are shown in blue (panels a and d), merged images presented in panels c and f. Large and multiple aggregates seen only in PINK1 kd neurons are positive for the dye Lysotracker (panel d). ,Scale bar = 20 mM doi:10.1371/journal.pone.0002455.g007 Table 1. Summary of the phenotypes observed with PINK1 deficiency in the different cell models used. Model SHSY5Y human Midbrain neurons human Cortical neurons mouse PINK1 deficiency shRNA shRNA Reduced viability Age-related Age-related Sensitivity to apoptosis Basal STS-induced Basal STS-induced Trans-genic Age-related Basal = not assessed doi:10.1371/journal.pone.0002455.t001 PLoS ONE | www.plosone.org 13 Mitochondria dysfunction QDym QDym Altered mitochondrial morphology qROS Q total glutathione Oxidative stress Lysosomal dysfunction qautophago-lysosomes q lysotracker uptake q lysotracker uptake June 2008 | Volume 3 | Issue 6 | e2455