RRC ID 45671
Author Ackema KB, Hench J, Böckler S, Wang SC, Sauder U, Mergentaler H, Westermann B, Bard F, Frank S, Spang A.
Title The small GTPase Arf1 modulates mitochondrial morphology and function.
Journal EMBO J
Abstract 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.
Volume 33(22)
Pages 2659-75
Published 2014-11-18
DOI 10.15252/embj.201489039
PII embj.201489039
PMID 25190516
PMC PMC4282574
MeSH ADP-Ribosylation Factor 1 / genetics ADP-Ribosylation Factor 1 / metabolism* Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* GTP Phosphohydrolases / genetics GTP Phosphohydrolases / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism Mitochondria / enzymology* Mitochondria / genetics Mitochondrial Membranes / enzymology Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Saccharomyces cerevisiae / enzymology* Saccharomyces cerevisiae / genetics Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism
IF 9.889
Times Cited 38
C.elegans tm1108 tm1133