Figure 5.

Defective Ca²⁺ handling, reduced mitochondrial copy number, and increased reticular stress in Stim1^R304W/+ slow-twitch muscle. (A,B) RT-qPCR on selected genes illustrates a reduction of SERCA1 gene expression and protein level and a simultaneous upregulation of the SERCA1 inhibitor Sln in Stim1^R304W/+ soleus, while other genes involved in Ca²⁺ handling are normally expressed (n = 4–5). (C,D) In agreement with the reduced protein level of the mitochondrial biogenesis regulator PGC1α in Stim1^R304W/+ soleus, the mitochondrial copy number marker genes mt16s, Cox2, and Loop are decreased compared with the WT (n = 4). (E,F) Oxygen consumption and ROS production are significantly lower in Stim1^R304W/+ compared with WT soleus (n = 7–8). (G) Increased UPR in Stim1^R304W/+ soleus as illustrated by the upregulation of the stress-regulated genes Hspa5, Hsp90b1, and Xbp1 (n = 4–5). (H,I) Stim1^R304W/+ soleus sections show a tendency of augmented apoptosis and a significant increase of regenerating fibers compared with controls (n = 3-5). Significant differences are illustrated as * (p < 0.05), ** (p < 0.01), *** (p < 0.001), and **** (p < 0.0001).