title: The abundance of the ARL2 GTPase and its GAP, ELMOD2, at mitochondria are modulated by the fusogenic activity of mitofusins and stressors.
abstract: Mitochondria are essential, dynamic organelles that respond to a number of stressors with changes in morphology that are linked to several mitochondrial functions, though the mechanisms involved are poorly understood. We show that the levels of the regulatory GTPase ARL2 and its GAP, ELMOD2, are specifically increased at mitochondria in immortalized mouse embryo fibroblasts deleted for Mitofusin 2 (MFN2), but not MFN1. Elevated ARL2 and ELMOD2 in MEFs deleted for MFN2 could be reversed by re-introduction of MFN2, but only when the mitochondrial fragmentation in these MEFs was also reversed, demonstrating that reversal of elevated ARL2 and ELMOD2 requires the fusogenic activity of MFN2. Other stressors with links to mitochondrial morphology were investigated and several, including glucose or serum deprivation, also caused increases in ARL2 and ELMOD2. In contrast, a number of pharmacological inhibitors of energy metabolism caused increases in ARL2 without affecting ELMOD2 levels. Together we interpret these data as evidence of two ARL2-sensitive pathways in mitochondria, one affecting ATP levels that is independent of ELMOD2 and the other leading to mitochondrial fusion involving MFN2 that does involve ELMOD2.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Newman
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Cara R
authors.initials: CR
authors.lastname: Schiavon
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Chengjing
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kahn
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000172:deficiency; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; C000622217:ELMOD2 protein, mouse; D000255:Adenosine Triphosphate; C485819:Arl2 protein, mouse; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C488750:Mfn1 protein, mouse; C488751:Mfn2 protein, mouse; D005947:Glucose