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EMBO J. 2014 Nov 18;33(22):2659-75. doi: 10.15252/embj.201489039. Epub 2014 Sep 4.

The small GTPase Arf1 modulates mitochondrial morphology and function.

Author information

1
Growth and Development, Biozentrum University of Basel, Basel, Switzerland.
2
Division of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland.
3
Cell Biology, University of Bayreuth, Bayreuth, Germany.
4
Institute for Molecular and Cell Biology, Singapore City, Singapore.
5
Microscopy Center, Biozentrum University of Basel, Basel, Switzerland.
6
Growth and Development, Biozentrum University of Basel, Basel, Switzerland anne.spang@unibas.ch.

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.

KEYWORDS:

Cdc48; ER–mitochondrial contact sites; mitochondria‐associated degradation; mitophagy; stress response

PMID:
25190516
PMCID:
PMC4282574
DOI:
10.15252/embj.201489039
[Indexed for MEDLINE]
Free PMC Article

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