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State of GTPase cycle dictates mobility and localization of large mitochondrial GTPases, Mfn1 and 2
Author(s) -
Cleland Megan Marie,
Ryu SeungWook,
Karbowski Mariusz,
Youle Richard
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a661-a
Subject(s) - mfn1 , mfn2 , mitochondrial fusion , microbiology and biotechnology , gtpase , mitochondrion , chemistry , fluorescence recovery after photobleaching , biophysics , biology , biochemistry , mitochondrial dna , membrane , gene
Mitochondria are dynamic organelles that are undergoing frequent fission and fusion events. The mitofusions, Mfn1 and Mfn2, mediate mitochondrial fusion. These proteins localize to distinct areas on the mitochondria and have been shown to tether the mitochondria together in both hetero‐ and homo‐dimeric complexes. We have found using FRAP (Fluorescence Recovery After Photobleaching) that mutants of mitofusins display markedly different mobilities on the mitochondrial membrane reflecting changes in complex formation. Mfn2‐K109T, a GTPase‐inactive mutant decreases FRAP recovery, whereas Mfn2‐rasG12V a dominant active GTPase mutant greatly increases FRAP recovery (Mfn2‐rasG12V>Mfn2>Mfn2‐K109T). These differences are supported by the mitochondrial localizations: Mfn2‐K109T is highly focal, while Mfn2‐rasG12V is more evenly distributed along the mitochondria. Conversely, Mfn1‐K88T, a GTPase mutant, increases FRAP recovery compared to Mfn1 and Mfn1‐rasG12V (Mfn1‐K88T>Mfn1rasG12V>Mfn1). Thus the submitochondrial localization and mobility on the mitochondrial membrane change as the two mitofusins transit through their GTPase cycles.