The small GTPase Arf1 modulates mitochondrial morphology and function

Area of Science:

• Cell Biology
• Molecular Biology
• Mitochondrial Biology

Background:

• The small GTPase Arf1 is known for its role in membrane traffic and protein coat recruitment.
• Its involvement in other cellular processes beyond vesicular transport remains largely unexplored.

Purpose of the Study:

• To investigate the potential role of Arf1 and its associated guanine nucleotide exchange factor (GBF1) in mitochondrial function.
• To determine if Arf1's mitochondrial role is conserved across different species and linked to specific cellular structures.

Main Methods:

• Utilized loss-of-function mutants in *Caenorhabditis elegans* and *Saccharomyces cerevisiae* to assess mitochondrial morphology and activity.
• Performed co-fractionation studies to examine the localization of yeast Arf1.
• Investigated genetic interactions between Arf1 and components of ER-mitochondrial contact sites.

Main Results:

• Loss of Arf1 or GBF1 function led to impaired mitochondrial morphology and activity in *C. elegans*, mammalian cells, and yeast.
• In yeast, Arf1 mutants showed accumulation of the mitofusin Fzo1, which was rescued by Cdc48 overexpression.
• Yeast Arf1 was found to co-fractionate with ER and mitochondrial membranes and genetically interact with Gem1, a contact site component.

Conclusions:

• Arf1 and GBF1 play a conserved, unexpected role in maintaining mitochondrial homeostasis and dynamics.
• This mitochondrial function of Arf1 is associated with ER-mitochondrial contacts and is independent of its canonical role in vesicular traffic.