Cardiolipin content, linoleic acid composition, and tafazzin expression in response to skeletal muscle overload and unload stimuli

Abstract

Cardiolipin (CL) is a unique mitochondrial phospholipid that, in skeletal muscle, is enriched with linoleic acid (18:2n6). Together, CL content and CL 18:2n6 composition are critical determinants of mitochondrial function. Skeletal muscle is comprised of slow and fast fibers that have high and low mitochondrial content, respectively. In response to overloading and unloading stimuli, these muscles undergo a fast-to-slow oxidative fiber type shift and a slow-to-fast glycolytic fiber type shift, respectively, with a concomitant change in mitochondrial content. Here, we examined changes in CL content and CL 18:2n6 composition under these conditions along with tafazzin (Taz) protein, which is a transacylase enzyme that generates CL lipids enriched with 18:2n6. Our results show that CL content, CL 18:2n6 composition, and Taz protein content increased with an overload stimulus in plantaris. Conversely, CL content and CL 18:2n6 composition was reduced with an unloaded stimulus in soleus. Interestingly, Taz protein was increased in the unloaded soleus, suggesting that Taz may provide some form of compensation for decreased CL content and CL 18:2n6 composition. Together, this study highlights the dynamic nature of CL and Taz in skeletal muscle, and future studies will examine the physiological significance behind the changes in CL content, CL 18:2n6 and Taz.

Assembly of the complexes of oxidative phosphorylation triggers the remodeling of cardiolipin

“…In summary, we have shown that the expression of OXPHOS complexes is a precondition for CL remodeling and that CL remodeling in turn is necessary for CL stability. This conclusion is supported by recent reports that show increased CL remodeling in response to muscle overload (increased OXPHOS expression) (55) and decreased CL remodeling in response to rapid cell proliferation (decreased OXPHOS expression) (56). Furthermore, the conclusion is consistent with the clinical presentation of Barth syndrome that afflicts organs, such as skeletal muscle and heart (30), which have high aerobic energy metabolism and, therefore, a high concentration of OXPHOS proteins.…”

Elevated whole muscle phosphatidylcholine: phosphatidylethanolamine ratio coincides with reduced SERCA activity in murine overloaded plantaris muscles

“…As previously reported, the overloaded plantaris muscles from the mice used in this study exhibited significant muscle hypertrophy with a 75% increase in muscle mass and a 1.8-fold increase in plantaris:body weight ratio [ 16 ]. In a recently published study, we showed that the increase in plantaris muscle mass due to the overload surgery was attributed to an increase in total myofibre number and cross-sectional area [ 10 ].…”

“…The mice used in this study were part of a previously published study examining changes in mitochondrial membrane lipid analyses in response to muscle overloading and unloading stimuli [ 16 ]. Specifically, six adult (4–6 month) male C57BL/6 mice (29.1 ± 1.2 g) were used and housed in an environmentally controlled room with a standard 12:12-h light-dark cycle and allowed access to food and water ad libitum.…”

“…To overload plantaris, mice were first anaesthetized with 2% isoflurane in a precision vaporizer. Next, soleus and gastrocnemius tendons were transected in one leg while the other contralateral leg served as a sham control [ 14 , 16 ]. Mice were then left for two weeks in individually housed cages to adapt as we have demonstrated previously that this time frame results in significant plantaris hypertrophy [ 16 ].…”

“…Next, soleus and gastrocnemius tendons were transected in one leg while the other contralateral leg served as a sham control [ 14 , 16 ]. Mice were then left for two weeks in individually housed cages to adapt as we have demonstrated previously that this time frame results in significant plantaris hypertrophy [ 16 ]. Subsequently, mice were anaesthetized in an induction chamber using isoflurane (5%), transitioned to a nose cone (5% isoflurane) and then placed on a surgical bed for muscles to be surgically removed.…”