Fig. 5: TDP-43 mislocalization impairs axonal and NMJ mitochondria via limitation of mitochondria-related protein synthesis. | Nature Communications

Fig. 5: TDP-43 mislocalization impairs axonal and NMJ mitochondria via limitation of mitochondria-related protein synthesis.

From: Axonal TDP-43 condensates drive neuromuscular junction disruption through inhibition of local synthesis of nuclear encoded mitochondrial proteins

Fig. 5

a Images and b quantification of TMRE signal in HB9::GFP MN axons untreated (control) or treated with anisomycin (aniso), cycloheximide (CHX) or NaAsO2. Scale bar=10 µm. n = 72,69,43,32 axons. Data are presented as mean values ± SD. One-way-ANOVA with Holm-Sidak correction. ****p < 0.0001. c Images and d quantification of OPP and mitochondria colocalization in TDP∆NLS or control MN axons. Scale bar=5 µm. n = 43,36 axons. Data are presented as mean values ± SD. Unpaired-t-test, two-sided ****p < 0.0001. e images and f quantification of mitochondria density within sciatic nerve longitudinal sections of TDP∆NLSThy1::MitoDendra and control mice labeled also for NFH and Tau. Scale bar=10 µm. n = 4,4 mice. Data are presented as mean values ± SEM. Unpaired-t-test, two-sided. ***p = 0.0001. g Images and h quantification of pre-synaptic mitochondrial volume within NMJs of TDP∆NLSThy1::MitoDendra and controlThy1::MitoDendra mice. BTX marks post-synapse. Scale bar=10 µm. n = 4,4 mice. Data are presented as mean values ± SEM. Unpaired-t-test, two-sided. ***p = 0.0001. i Images and j quantification of pre-synaptic TMRE signal intensity within in vitro NMJs from TDP∆NLSThy1::MitoDendra, controlThy1::MitoDendra co-cultures and TDP∆NLSThy1::MitoDendra co-cultures treated with G3BP1 peptides in NMJ compartment. Scale bar=10 µm. n = 40,51,45 NMJs. One-way-ANOVA with Holm-Sidak correction. Data are presented as mean values ± SD. **p = 0.0034, ***p = 0.0005. a.u stands for arbitrary units. Source data are provided as a Source Data file.

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