Single Muscle Fiber Proteomics Reveals Distinct Protein Changes in Slow and Fast Fibers during Muscle Atrophy

Skeletal muscles are composed of heterogeneous collections of fibers with different metabolic profiles. With varied neuronal innervation and fiber-type compositions, each muscle fulfils specific functions and responds differently to stimuli and perturbations. We assessed individual fibers by mass spectrometry to dissect protein changes after loss of neuronal innervation due to section of the sciatic nerve in mice. This proteomics approach enabled us to quantify ∼600 proteins per individual soleus and EDL ( extensor digitorum longus) musclefiber. Expression of myosin heavy chain (MyHC) in individual fibers enabled clustering of specific fiber types; comparison of fibers from control and denervatedmuscles with the same MyHC expression revealed restricted regulation of a total of 240 proteins in type-I, -IIa, or -IIb fibers 7 days after denervation. The levels of several mitochondrial and proteasomal proteins were significantly altered, indicating rapid adaption of metabolic processes after denervation. Fur...