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Updated: May 23, 2025

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

Yungui Guo1, David Brooks1, Ziwei Zhao1

  • 1Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS, USA.

Autophagy Reports
|May 21, 2025
PubMed

Insights

Pavarotti (Pav) and Tumbleweed (Tum) proteins are involved in nuclear envelope budding. Blocking this process leads to mitochondrial dysfunction and autophagosome formation in muscle cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Pavarotti (Pav) and Tumbleweed (Tum) are crucial for microtubule-dependent movements in cytokinesis.
  • Their roles beyond cytokinesis, particularly in muscle cells, are less understood.

Purpose of the Study:

  • To investigate the function of the Pav-Tum complex in post-mitotic muscle cells.
  • To explore the relationship between nuclear envelope budding and cellular homeostasis.

Main Methods:

  • RNA interference (RNAi) to knock down Pav, Marf, Wash, and Torsin in Drosophila muscles.
  • Immunofluorescence microscopy to detect ubiquitin, p62, and Atg8a.
  • Analysis of microtubule organization and mitochondrial localization.

Main Results:

  • Pav knockdown in muscles unexpectedly led to the accumulation of ubiquitin, p62, and Atg8a puncta without microtubule disorganization.
  • Autophagosomal structures and mitochondria clustered together.
  • Pav-Tum localized to muscle nuclei, suggesting a role in nuclear envelope (NE) budding.
  • Knockdown of NE budding components (Marf, Wash, Torsin) also caused mitochondrial clustering.

Conclusions:

  • The Pav-Tum complex plays a role in nuclear envelope budding in muscle cells.
  • Inhibition of NE budding disrupts mitochondrial function and triggers autophagosome formation.
  • This study reveals a novel link between NE budding, mitochondrial health, and autophagy in muscle.
Keywords:
D. melanogasterMuscleNuclear envelope buddingautophagosomemitochondria

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