Degradation
Protease: enzyme that degrades proteins, begins protein catabolism
Calcium activates enzymes which are involved in the degradation of muscle proteins
o Changes in Ca2+ flux can also initiate mitochondrial biogenesis
E3 ligases: MAFbx, MuRF1, Atrogin-1
o Muscle atrophy/disuse associated with an upregulation of both ligases
o Denervation stimulates expression of MAFbx and MurF1 muscle atrophy
Calpains: calcium activated proteinase in cytosol of cell
o Degrades scaffolding proteins such as titin, vinculin, nebulin
o Breakdown cytoskeleton
o Activity increases during unloading (decrease in desmin means the cytoskeleton is being
broken down)
Caspases: cytosolic proteases involved in protein breakdown and apoptosis
o During muscle disuse, caspases will go into nucleus and break down DNA
Lysosomal proteolysis: “suicide bags” – proteins enter lysosomes via endocytosis and contain
cathespins (protease that degrades proteins), nucleases, and proteases that degrade bonds in an
acid environment
o Degrades all types of proteins (receptors, ligands, DNA, RNA)
Ubiquitin-Proteasome: “the inverse of transcription” – principle mechanism for protein catabolism
in the cytosol and nucleus
o E1, E2, E3 ligases and the ubiquitin goes through each step and binds with itself
o All ubiquitin’s bind with a protein and once that happens the protein becomes a marker for
26S proteasome to break it down E3 ligases is most crucial step because it binds all
ubiquitin to protein
o Atrogin-1: an E3 ligase that is highly expressed during muscle atrophy
o Is ATP dependent
Reactive oxygen and nitrogen species (RONS): one source is production from mitochondria and has
a negative effect (degradation)
o Muscle disuse will stimulate ROS production increases calcium concentration
Myostatin: a protein that acts on muscle cells' autocrine function to inhibit myogenesis (muscle cell
growth and differentiation), is a member of the TGF-β protein family
o Inhibits rate of translation (through Akt inhibition)
o Inhibits rate of mRNA transcription
o Inhibits proliferation and fusion of satellite cells (inhibits regeneration)
o Increases proteasome activity reduces protein synthesis, stimulates protein degradation
(means it increases E3 ligases)
o Expression levels of myostatin mRNA are not altered during aging
Tumor necrosis factor (TNFα): a cell signaling protein (cytokine) involved in systemic inflammation
o Chiefly activated by macrophages
o Regulates immune cells, induces fever, apoptotic cell death, cachexia (loss of body mass that
cannot be reversed nutritionally), and inflammation
o Responds to signals from IL-6
o Increases during aging
Proliferation
Protease: enzyme that degrades proteins, begins protein catabolism
Calcium activates enzymes which are involved in the degradation of muscle proteins
o Changes in Ca2+ flux can also initiate mitochondrial biogenesis
E3 ligases: MAFbx, MuRF1, Atrogin-1
o Muscle atrophy/disuse associated with an upregulation of both ligases
o Denervation stimulates expression of MAFbx and MurF1 muscle atrophy
Calpains: calcium activated proteinase in cytosol of cell
o Degrades scaffolding proteins such as titin, vinculin, nebulin
o Breakdown cytoskeleton
o Activity increases during unloading (decrease in desmin means the cytoskeleton is being
broken down)
Caspases: cytosolic proteases involved in protein breakdown and apoptosis
o During muscle disuse, caspases will go into nucleus and break down DNA
Lysosomal proteolysis: “suicide bags” – proteins enter lysosomes via endocytosis and contain
cathespins (protease that degrades proteins), nucleases, and proteases that degrade bonds in an
acid environment
o Degrades all types of proteins (receptors, ligands, DNA, RNA)
Ubiquitin-Proteasome: “the inverse of transcription” – principle mechanism for protein catabolism
in the cytosol and nucleus
o E1, E2, E3 ligases and the ubiquitin goes through each step and binds with itself
o All ubiquitin’s bind with a protein and once that happens the protein becomes a marker for
26S proteasome to break it down E3 ligases is most crucial step because it binds all
ubiquitin to protein
o Atrogin-1: an E3 ligase that is highly expressed during muscle atrophy
o Is ATP dependent
Reactive oxygen and nitrogen species (RONS): one source is production from mitochondria and has
a negative effect (degradation)
o Muscle disuse will stimulate ROS production increases calcium concentration
Myostatin: a protein that acts on muscle cells' autocrine function to inhibit myogenesis (muscle cell
growth and differentiation), is a member of the TGF-β protein family
o Inhibits rate of translation (through Akt inhibition)
o Inhibits rate of mRNA transcription
o Inhibits proliferation and fusion of satellite cells (inhibits regeneration)
o Increases proteasome activity reduces protein synthesis, stimulates protein degradation
(means it increases E3 ligases)
o Expression levels of myostatin mRNA are not altered during aging
Tumor necrosis factor (TNFα): a cell signaling protein (cytokine) involved in systemic inflammation
o Chiefly activated by macrophages
o Regulates immune cells, induces fever, apoptotic cell death, cachexia (loss of body mass that
cannot be reversed nutritionally), and inflammation
o Responds to signals from IL-6
o Increases during aging
Proliferation
