title: The small GTPase Arf1 modulates mitochondrial morphology and function.
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.
authors.affiliation: Growth and Development, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Karin B
authors.initials: KB
authors.lastname: Ackema
authors.affiliation: Division of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hench
authors.affiliation: Cell Biology, University of Bayreuth, Bayreuth, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Böckler
authors.affiliation: Institute for Molecular and Cell Biology, Singapore City, Singapore.
authors.forename: Shyi Chyi
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Microscopy Center, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Sauder
authors.affiliation: Growth and Development, Biozentrum University of Basel, Basel, Switzerland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Mergentaler
authors.affiliation: Cell Biology, University of Bayreuth, Bayreuth, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Westermann
authors.affiliation: Institute for Molecular and Cell Biology, Singapore City, Singapore.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bard
authors.affiliation: Division of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Frank
authors.affiliation: Growth and Development, Biozentrum University of Basel, Basel, Switzerland anne.spang@unibas.ch.
authors.forename: Anne
authors.initials: A
authors.lastname: Spang
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D051336:Mitochondrial Membranes / Q000201:enzymology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C120472:GEM1 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins; C401395:FZO1 protein, S cerevisiae; D020558:GTP Phosphohydrolases; D020823:ADP-Ribosylation Factor 1
keywords: Cdc48; ER–mitochondrial contact sites; mitochondria‐associated degradation; mitophagy; stress response