Fourteen-week-old Tak1^fl/fl and Tak1^mKO mice were given i.p. injections of tamoxifen. After 10 weeks, the mice were euthanized and skeletal muscles were collected and processed for histological and biochemical analysis. (A) Longitudinal muscle sections prepared from soleus muscle of Tak1^fl/fl and Tak1^mKO mice were processed for transmission electron microscopy (TEM) analysis. Representative EM images featuring intermyofibrillar (top panel) and subsarcolemmal (lower panel) mitochondria are presented here. Scale bars: 1 μm. (B) Higher-magnification EM images depicting vacuolated mitochondria in soleus muscle of Tak1^mKO mice. Scale bars: 0.5 μm. Mitochondria were isolated from GA muscle of Tak1^fl/fl and Tak1^mKO mice, and state 3 and state 4 respiration was measured by respirometry . Oxygen consumption rate (OCR) was measured in the presence of (C) glutamate/malate and (D) succinate. n = 6 in each group from A–D. Error bars represent ± SD. *P < 0.05 values significantly different from corresponding Tak1^fl/fl mice by unpaired t test. (E) Representative immunoblots of Mitofusin-2, Drp1, Pink1, LC3B-I/II, Beclin-1, p62, and unrelated protein GAPDH in mitochondrial fraction of GA muscle of Tak1^fl/fl and Tak1^mKO mice. (F) Representative immunoblot depicting the levels of irreversibly oxidized (carbonylated) protein in GA muscle of Tak1^fl/fl and Tak1^mKO mice. (G) Densitometry quantification of oxidized proteins. (H) Relative mRNA levels of oxidative stress related genes catalase (CAT), glutathione peroxidase 1 (GPx1), xanthine dehydrogenase (XDH), copper- and zinc–containing SOD (Cu/ZnSOD), extracellular SOD (EcSOD), and manganese SOD (MnSOD) by qPCR in skeletal muscle of Tak1^fl/fl and Tak1^mKO mice. n = 5 or 6 in each group. Error bars represent ± SEM. *P < 0.05, values significantly different from corresponding Tak1^fl/fl mice by unpaired 2-tailed t test.