Details

Autor(en) / Beteiligte

• Ackema, Karin B
• Hench, Jürgen
• Böckler, Stefan
• Wang, Shyi Chyi
• Sauder, Ursula
• Mergentaler, Heidi
• Westermann, Benedikt
• Bard, Frédéric
• Frank, Stephan
• Spang, Anne

Titel

The small GTP ase Arf1 modulates mitochondrial morphology and function

Ist Teil von

• The EMBO journal, 2014-11, Vol.33 (22), p.2659-2675

Erscheinungsjahr

2014

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Abstract The small GTP ase Arf1 plays critical roles in membrane traffic by initiating the recruitment of coat proteins and by modulating the activity of lipid‐modifying enzymes. Here, we report an unexpected but evolutionarily conserved role for Arf1 and the Arf GEF GBF 1 at mitochondria. Loss of function of ARF ‐1 or GBF ‐1 impaired mitochondrial morphology and activity in Caenorhabditis elegans . Similarly, mitochondrial defects were observed in mammalian and yeast cells. In Saccharomyces cerevisiae , aberrant clusters of the mitofusin Fzo1 accumulated in arf1‐11 mutants and were resolved by overexpression of Cdc48, an AAA ‐ ATP ase involved in ER and mitochondria‐associated degradation processes. Yeast Arf1 co‐fractionated with ER and mitochondrial membranes and interacted genetically with the contact site component Gem1. Furthermore, similar mitochondrial abnormalities resulted from knockdown of either GBF ‐1 or contact site components in worms, suggesting that the role of Arf1 in mitochondrial functioning is linked to ER –mitochondrial contacts. Thus, Arf1 is involved in mitochondrial homeostasis and dynamics, independent of its role in vesicular traffic. Synopsis image The GTP ase Arf1 and its GEF GBF ‐1/Gea1/2 have a role independent of the well known regulation of vesicle trafficking in maintaining mitochondrial dynamics and function via Cdc48 and mitofusin mediated quality control and ER ‐mitochondria contact site functionality. The Arf GEF GBF ‐1/Gea1/2 and Arf1 are required for mitochondrial dynamics and function from yeast to man. Arf1 localizes to mitochondria or mitochondria‐associated membranes in yeast. Loss of Arf1 activity causes aggregation of the mitofusin Fzo1. Arf1 interacts with the AAA ‐ ATP ase Cdc48, which removes misfolded Fzo1 from mitochondrial membranes.