The small GTPase Arf1 modulates mitochondrial morphology and function.
EMBO J
; 33(22): 2659-75, 2014 Nov 18.
Article
em En
| MEDLINE
| ID: mdl-25190516
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.
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MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Caenorhabditis elegans
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Fator 1 de Ribosilação do ADP
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Proteínas de Caenorhabditis elegans
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article