Study summary · research use only
MOTS-c modulates skeletal muscle function by directly binding and activating CK2
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This laboratory and mouse study examined whether CK2 is a direct target of the mitochondrial microprotein MOTS-c in skeletal muscle. MOTS-c was reported to bind directly to CK2 and activate it in cell-free systems. In mice, MOTS-c administration was associated with prevention of skeletal muscle atrophy and increased muscle glucose uptake, effects reported to be blunted by suppressing CK2 activity; effects were tissue-specific, stimulating CK2 activity in muscle while suppressing it in fat. A naturally occurring variant, K14Q MOTS-c, showed reduced CK2 binding and did not activate CK2. In a human genetic analysis, male K14Q MOTS-c carriers had a higher reported risk of sarcopenia and type 2 diabetes (T2D) depending on age and activity, while female carriers had an age-specific reduced reported risk of T2D.
Abstract
MOTS-c is a mitochondrial microprotein that improves metabolism. Here, we demonstrate CK2 is a direct and functional target of MOTS-c. MOTS-c directly binds to CK2 and activates it in cell-free systems. MOTS-c administration to mice prevented skeletal muscle atrophy and enhanced muscle glucose uptake, which were blunted by suppressing CK2 activity. Interestingly, the effects of MOTS-c are tissue-specific. Systemically administered MOTS-c binds to CK2 in fat and muscle, yet stimulates CK2 activity in muscle while suppressing it in fat by differentially modifying CK2-interacting proteins. Notably, a naturally occurring MOTS-c variant, K14Q MOTS-c, has reduced binding to CK2 and does not activate it or elicit its effects. Male K14Q MOTS-c carriers exhibited a higher risk of sarcopenia and type 2 diabetes (T2D) in an age- and physical-activity-dependent manner, whereas females had an age-specific reduced risk of T2D. Altogether, these findings provide evidence that CK2 is required for MOTS-c effects.
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