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)
muscle fiber. Expression of myosin heavy chain (MyHC) in individual
fibers enabled clustering of specific fiber types; comparison of fibers
from control and denervated muscles 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.
Furthermore, we observed fiber-type-specific regulation of proteins
involved in calcium ion binding and transport, such as troponins,
parvalbumin, and ATP2A2, indicating marked remodeling of muscle contractility
after denervation. This study provides novel insight into how different
muscle fiber types remodel their proteomes during muscular atrophy.