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PLoS One. 2014 Jun 9;9(6):e99270. doi: 10.1371/journal.pone.0099270. eCollection 2014.

The ARL2 GTPase is required for mitochondrial morphology, motility, and maintenance of ATP levels.

Author information

1
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
2
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
3
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
4
Consiglio Nazionale delle Ricerche Institute of Biomembranes and Bioenergetics, Bari, Italy.
5
Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, Bari, Italy.

Abstract

ARF-like 2 (ARL2) is a member of the ARF family and RAS superfamily of regulatory GTPases, predicted to be present in the last eukaryotic common ancestor, and essential in a number of model genetic systems. Though best studied as a regulator of tubulin folding, we previously demonstrated that ARL2 partially localizes to mitochondria. Here, we show that ARL2 is essential to a number of mitochondrial functions, including mitochondrial morphology, motility, and maintenance of ATP levels. We compare phenotypes resulting from ARL2 depletion and expression of dominant negative mutants and use these to demonstrate that the mitochondrial roles of ARL2 are distinct from its roles in tubulin folding. Testing of current models for ARL2 actions at mitochondria failed to support them. Rather, we found that knockdown of the ARL2 GTPase activating protein (GAP) ELMOD2 phenocopies two of three phenotypes of ARL2 siRNA, making it a likely effector for these actions. These results add new layers of complexity to ARL2 signaling, highlighting the need to deconvolve these different cell functions. We hypothesize that ARL2 plays essential roles inside mitochondria along with other cellular functions, at least in part to provide coupling of regulation between these essential cell processes.

PMID:
24911211
PMCID:
PMC4050054
DOI:
10.1371/journal.pone.0099270
[Indexed for MEDLINE]
Free PMC Article

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