Myofibrils are long intracellular cables specific to muscles, composed mainly of actin
and myosin filaments. The actin and myosin filaments are organized into repeated units
called sarcomeres, which form the myofibrils. Muscle contraction is achieved by the
simultaneous shortening of sarcomeres, which requires all sarcomeres to be the same
size. Muscles have a variety of ways to ensure sarcomere homogeneity. We have previously
shown that the controlled oligomerization of Zasp proteins sets the diameter of the
myofibril. Here, we looked for Zasp-binding proteins at the Z-disc to identify additional
proteins coordinating myofibril growth and assembly. We found that the E1 subunit
of the oxoglutarate dehydrogenase complex localizes to both the Z-disc and the mitochondria,
and is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase
complex are required for myofibril formation. Using super-resolution microscopy, we
revealed the overall organization of the complex at the Z-disc. Metabolomics identified
an amino acid imbalance affecting protein synthesis as a possible cause of myofibril
defects, which is supported by OGDH-dependent localization of ribosomes at the Z-disc.
