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. 2019 Aug;10(8):610-614.
doi: 10.1007/s13238-019-0621-4.

VHL-1 inactivation and mitochondrial antioxidants rescue C. elegans dopaminergic neurodegeneration

Song Chen  1   2 , Shuo Luo  1 , Zhe Zhang  1 , Dengke K Ma  3
Affiliations

VHL-1 inactivation and mitochondrial antioxidants rescue C. elegans dopaminergic neurodegeneration

Song Chen et al. Protein Cell. 2019 Aug.
No abstract available

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Figures

Figure 1
Figure 1
Genetic and pharmacological rescue of complex I-dysfunction induced ADE neurodegeneration. (A) Schematic illustrating the four CEP, two ADE dopaminergic and two non-dopaminergic AIY neurons. (B) Exemplar confocal fluorescence images of L4-stage transgenic strains with the markers otIs181 and zcIs9 to monitor dopamine neuron morphologies and mito-UPR, respectively, in the wild-type genetic background. (C) Merged GFP, mCherry and phase-contrast (up) and mCherry only (down) epifluorescence whole-body images showing intact CEP, ADE and AIY neurons, marked by mCherry, and absence of mito-UPR, marked by GFP in L4-stage wild type animals. (D) Exemplar images taken under the same condition as in (C) showing intact CEP and AIY, loss of ADE neurons and constitutive mito-UPR in L4-stage nduf-7(et19) mutants. (E) Exemplar images taken under the same condition as in (C) showing intact CEP and AIY, rescued ADE neurons and constitutive mito-UPR in L4-stage nduf-7(et19); vhl-1(ok161) double mutants. (F) Exemplar confocal images showing progressive age-dependent ADE neurodegeneration. (G) Quantification of ADE neurodegeneration in various strains of indicated genotype and with pharmacological treatments. Vehicle-only control is similar to that without pharmacological treatments. Both mitoQ and trolox were applied to the culture plates (0.3 and 3 mg/mL, respectively) with exposure to animals at 20 °C before scoring ADE neurons. ***P < 0.001, ANOVA; n ≥ 3 biological replicates with animal numbers of each group ≥30. Scale bars, 50 µm
Figure 2
Figure 2
VHL-1 inactivation rescues impaired mitochondrial respiratory activity in nduf-7 mutants. (A) Exemplar confocal images showing MitoSOX Red staining of posterior pharyngeal bulbs (circled dash line). The CEP, ADE and AIY neurons are labeled by dat-1p::mCherry reporter transgenes and are also red fluorescent, precluding direct MitoSOX measurements in neurons. For each genotype (Wild type, nduf-7, nduf-7; vhl-1, and nduf-7_-Ve, with vehicle only control), twenty L4-stage animals were transferred to MitoSOX Red plates seeded with 100 mL of OP50 E. coli supplemented with 50 μmol/L MitoSOX Red (M36008, ThermoFisher Scientific) and incubated for 24 h at 20 °C in darkness. Confocal images of animal’s posterior pharyngeal bulb were processed in ImageJ and fluorescence intensity of maximal z-projection of posterior pharyngeal bulbs was measured individually. Scale bars: 25 µm. (B) Quantification of MitoSOX Red staining of posterior pharyngeal bulbs in various strains of indicated genotype and conditions. Bars represent mean ± S.E.M. **P < 0.01; ***P < 0.001, ANOVA
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References

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