Polarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport

Youjun Wu1,2, Chen Ding1,2, Behrang Sharif3,4

  • 1Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.

PubMed

Insights

Mitochondria transport in neurons relies on kinesin-1 and RIC-7, which work together at the mitochondrial leading edge for anterograde axonal transport in C. elegans.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Molecular Motors

Background:

  • Mitochondria transport is essential for neuronal function, involving kinesin-1 and dynein motor complexes.
  • Miro and Milton/TRAK are known adaptors for kinesin-1, but other mechanisms may exist.
  • RIC-7 is a C. elegans gene critical for axonal mitochondria localization, independent of kinesin-1.

Purpose of the Study:

  • To elucidate the role of RIC-7 in axonal mitochondria transport.
  • To investigate the interplay between RIC-7, Miro, and kinesin-1 in mitochondrial trafficking.
  • To identify the molecular mechanisms governing anterograde mitochondrial transport.

Main Methods:

  • CRISPR engineering in C. elegans to study gene functions.
  • Analysis of mitochondrial localization and transport dynamics.
  • Biochemical assays to determine protein interactions and domain requirements.

Main Results:

  • Miro is important for retrograde but not essential for anterograde mitochondrial transport.
  • Endogenous RIC-7 and kinesin-1 collaborate at the leading edge for anterograde transport.
  • RIC-7 mitochondrial binding involves its N-terminal domain and MIRO-1, while accumulation depends on its disordered region, kinesin-1, and metaxin2.

Conclusions:

  • Kinesin-1 and RIC-7 form transport complexes that polarize at the mitochondrial leading edge.
  • These complexes are crucial for anterograde axonal transport of mitochondria in C. elegans.
  • RIC-7 represents a key component in the machinery for mitochondrial distribution within axons.

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