ATAD2 is a Novel Regulator of Myogenesis and Autophagy in Skeletal Muscles

Using immunoprecipitation assay, we found that the nuclear protein ATAD2 (ATPase family AAA domain containing 2) interacts with MYTHO protein in C2C12 myoblasts. The functional role of ATAD2 in skeletal muscle cells was assessed by using transient and stable Atad2 knockdown (KD) in C2C12 myoblasts.

Atad2 KD significantly increased myoblast proliferation rate, S-phase entry, overall cell viability, and early differentiation into myotubes. However, Atad2 KD also elicited myotube atrophy and accumulation of autophagy-related proteins due to inhibition of autophagosome fusion with lysosomes and/or lysosome dysfunction. LAMP1 staining confirmed the presence of enlarged lysosomes in Atad2 KD cells.