Fig. 1: α-synuclein causes mitochondrial fragmentation independent of the C-terminus. | Cell Death & Disease

Fig. 1: α-synuclein causes mitochondrial fragmentation independent of the C-terminus.

From: Differential mitochondrial roles for α-synuclein in DRP1-dependent fission and PINK1/Parkin-mediated oxidation

Fig. 1

A Schematic diagram of the larval nervous system. Schematic diagram of the 140aa α-syn showing the α-helical amphipathic domain, the non-amyloidogenic component region (NAC) and the acidic C-terminal region. Representative images from larval segmental nerves from wild type (WT) and larva expressing human α-synWT, excess α-syn (α-synLP3), α-synΔNAC (deletion of aa71–82 (NAC), and α-syn1–120 (deletion of aa121–140) immunostained with the mitochondria marker cytochrome C (cyt C). Scale bar = 10 µm. B Quantification of the avg. mitochondria area (µm2) per larvae revealed the extent of mitochondrial fragmentation. Larvae expressing α-synWT (p < 0.001) and α-synLP3 (p < 0.0001) showed a significant reduction in mitochondria areas compared to WT. Note that the avg. mitochondria area of α-synLP3 larvae were found to be significantly decreased compared to α-synWT (p < 0.01). Further, larvae expressing α-synΔNAC (p < 0.01) or α-syn1–120 (p < 0.01) also showed a significant reduction in mitochondria areas compared to α-synWT, similar to α-synLP3. C Representative images from segmental nerves of larva expressing α-synWT-eGFP alone or larva expressing α-synWT-eGFP in the context of excess HSP70. Scale bar = 10 µm. Quantification of the avg. number of α-synWT-eGFP blockages per larvae (#) revealed a significant reduction in blockages with excess HSP70 compared to α-synWT-eGFP alone (p < 0.01). D Representative images from segmental nerves from WT and larva expressing α-synWT, α-synWT-eGFP, or α-synWT-eGFP in the context of excess HSP70 that have been immunostained with cyt C. Scale bar = 10 µm. Quantification of the avg. mitochondria area (µm2) per larvae revealed that larvae expressing either α-synWT-eGFP or α-synWT-eGFP in the context of excess HSP70 were found to be significantly decreased compared to WT (p < 0.01) and similar to larva expressing α-synWT (ns). n = 6 larvae, >250 mitochondria. Statistical significance was determined using the two-sample two-sided Student’s t test. *p < 0.01, **p < 0.001, ***p < 0.0001, ****p < 0.00001.

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