The oxoglutarate dehydrogenase complex is involved in myofibril growth and Z-disc assembly in Drosophila

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 Zaspoinding proteins at the Z-disc to identif y 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 oxoglutar a t e 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.

Automated summary

Myofibrils are intracellular cables specific to muscles composed of actin and myosin filaments. Sarcomeres, repeated units of actin and myosin filaments, form myofibrils. Zasp proteins control the diameter of myofibrils and the E1 subunit of the oxoglutarate dehydrogenase complex is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase complex are necessary for myofibril formation and an amino acid imbalance affecting protein synthesis may cause myofibril defects.