Fis1, DLP1, and Pex11p coordinately regulate peroxisome morphogenesis

Area of Science:

• Cell Biology
• Molecular Biology
• Organelle Dynamics

Background:

• Peroxisome division and morphology are vital cellular processes.
• Dynamin-like protein 1 (DLP1) and Pex11pbeta are known regulators of peroxisome morphogenesis.
• The role of Fis1 in peroxisome fission remained largely uncharacterized.

Purpose of the Study:

• To investigate the involvement of Fis1 in peroxisome fission.
• To elucidate the interaction of Fis1 with other known peroxisome division proteins.
• To determine the functional domains of Fis1 and Pex11pbeta in peroxisome division.

Main Methods:

• Immunofluorescence microscopy to detect endogenous Fis1 localization.
• Subcellular fractionation to confirm Fis1 presence in peroxisomes.
• Co-immunoprecipitation and chemical cross-linking to analyze protein interactions.
• RNA interference and ectopic expression to study the functional impact of Fis1 and Pex11pbeta.

Main Results:

• Endogenous Fis1 localizes to both peroxisomes and mitochondria, with a C-tail anchored membrane topology.
• Ectopic FIS1 expression promotes peroxisome proliferation, while FIS1 RNA interference leads to peroxisome tubulation.
• Fis1 directly binds to Pex11pbeta, and ternary complexes of Fis1, Pex11pbeta, and DLP1 are formed.
• The N-terminal domain of Pex11pbeta is essential for its homo-oligomerization and peroxisome proliferation activity.

Conclusions:

• Fis1 plays a significant role in peroxisome division and morphology maintenance in mammalian cells.
• Fis1 likely functions in concert with Pex11pbeta and DLP1 to regulate peroxisome fission.
• Understanding these interactions provides insights into the complex machinery governing organelle dynamics.