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. Author manuscript; available in PMC: 2014 Mar 6.
Published in final edited form as: Neuron. 2013 Mar 6;77(5):886–898. doi: 10.1016/j.neuron.2013.01.012

Figure 2. SC mitochondrial dysfunction activates a maladaptive integrated stress response (ISR).

Figure 2

(A) SC mitochondrial dysfunction upregulates the expression of ISR target genes in 2-month-old Tfam-SCKO nerves compared to Ctrl as measured by qRT-PCR. ATF4, activating transcription factor 4; Ddit3, DNA-damage inducible transcript 3; ASNS, asparagine synthetase; MTHFD2, methylenetetrahydrofolate dehydrogenase; TRIB3, tribbles homolog 3. N=5 mice per genotype. *P<0.05 (B) Immunoblot analysis shows increased phosphorylation of eIF2α in 2-month-old Tfam-SCKO vs. Ctrl nerves, confirming the activation of the ISR (C) Inhibition of mitochondrial respiration in cultured SCs with mitochondrial inhibitors upregulates the expression of ISR target genes as measured by qRT-PCR. N=duplicate wells from 3 independent experiments. *P<0.05. (D) Immunoblot analysis shows that application of the mitochondrial inhibitor CCCP to cultured SCs increases phosphorylation of eIF2α, indicating that inhibition of the mitochondrial electron transport chain activates the ISR.