Loss of nuclear envelope bud formation leads to mitophagy initiation in muscles.

Pavarotti (Pav) and its binding partner Tumbleweed (Tum) are well known for their evolutionarily conserved roles in microtubule-dependent movements during cytokinesis. In post-mitotic muscles, we unexpectedly observed the accumulation of puncta marked by ubiquitin, p62, and Atg8a without an obvious disorganization of the microtubule network. Some of these autophagosomal structures clustered together and colocalized with mitochondria. The Pav-Tum complex was enriched in muscle nuclei, consistent with roles for Pav and Tum in nuclear envelope (NE) budding, an alternative pathway for the export of large ribonucleoproteins. One of the established cargoes of the NE budding pathway, , was indeed reduced in the myoplasm of muscles. Moreover, RNAi knockdown of Marf or the NE budding components Wash or Torsin also caused the clustering of p62-marked mitochondria. These data together define a model whereby blocking NE budding reduces mitochondrial activity and in turn recruits p62 and autophagic structures for a lysosomal fate.