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

## TL;DR

This study shows that disrupting nuclear envelope budding in fruit fly muscles leads to the activation of mitophagy, a process that clears damaged mitochondria.

## Contribution

The paper reveals a novel link between nuclear envelope budding and mitophagy initiation in Drosophila muscles.

## Key findings

- Blocking nuclear envelope budding reduces Marf mRNA levels in muscle cells.
- RNAi knockdown of NE budding components causes p62-marked mitochondrial clustering.
- Mitochondrial dysfunction from NE budding disruption triggers autophagy for lysosomal degradation.

## Abstract

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 pav RNAi 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 Drosophila NE budding pathway, Marf mRNA, was indeed reduced in the myoplasm of pav RNAi 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.