The small GTPase Arf1 modulates mitochondrial morphology and function

作者：Ackema Karin B; Hench Juergen; Boeckler Stefan; Wang Shyi Chyi; Sauder Ursula; Mergentaler Heidi; Westermann Benedikt; Bard Frederic; Frank Stephan; Spang Anne^*

来源：The EMBO Journal, 2014, 33(22): 2659-2675.

DOI：10.15252/embj.201489039

• Cdc48
• ER-mitochondrial contact sites
• mitochondria-associated degradation
• mitophagy
• stress response

The small GTPase 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 ArfGEF GBF1 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-ATPase 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.

• 出版日期2014-11-18