βIII-Tubulin Structural Domains Regulate Mitochondrial Network Architecture in an Isotype-Specific Manner

Amelia L. Parker, Wee Siang Teo, Simon Brayford, Ullhas K. Moorthi, Senthil Arumugam, Charles Ferguson, Robert G. Parton, Joshua A. McCarroll, Maria Kavallaris

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2 Citations (Scopus)

Abstract

βIII-tubulin is a neuronal microtubule protein that is aberrantly expressed in epithelial cancers. The microtubule network is implicated in regulating the architecture and dynamics of the mitochondrial network, although the isotype-specific role for β-tubulin proteins that constitute this microtubule network remains unclear. High-resolution electron microscopy revealed that manipula-tion of βIII-tubulin expression levels impacts the volume and shape of mitochondria. Analysis of the structural domains of the protein identifies that the C-terminal tail of βIII-tubulin, which distin-guishes this protein from other β-tubulin isotypes, significantly contributes to the isotype-specific effects of βIII-tubulin on mitochondrial architecture. Mass spectrometry analysis of protein–protein interactions with β-tubulin isotypes identifies that βIII-tubulin specifically interacts with regulators of mitochondrial dynamics that may mediate these functional effects. Advanced quantitative dynamic lattice light sheet imaging of the mitochondrial network reveals that βIII-tubulin promotes a more dynamic and extended reticular mitochondrial network, and regulates mitochondrial volume. A reg-ulatory role for the βIII-tubulin C-terminal tail in mitochondrial network dynamics and architecture has widespread implications for the maintenance of mitochondrial homeostasis in health and disease.

Original languageEnglish
Article number776
Number of pages18
JournalCells
Volume11
Issue number5
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • Carboxy-terminal tail
  • Microtubules
  • Mitochondria
  • Tubulin isotype

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