Abstract
Miro GTPase, a member of the Ras superfamily, consists of two GTPase domains flanking a pair of EF hand motifs and a C-terminal transmembrane domain that anchors the protein to the mitochondrial outer membrane. Since the identification of Miro in humans, a series of studies in metazoans, including mammals and fruit flies, have shown that Miro plays a role in the calcium-dependent regulation of mitochondrial transport along microtubules. However, in non-metazoans, including yeasts, slime molds, and plants, Miro is primarily involved in the maintenance of mitochondrial morphology and homeostasis. Given the high level of conservation of Miro in eukaryotes and the variation in the molecular mechanisms of mitochondrial transport between eukaryotic lineages, Miro may have a common ancestral function in mitochondria, and its roles in the regulation of mitochondrial transport may have been acquired specifically by metazoans after the evolutionary divergence of eukaryotes.
Highlights
Mitochondria are essential organelles for aerobic energy production and metabolism in eukaryotic cells
The translocase of the outer mitochondrial membrane (TOM) complex is the main pathway for mitochondrial protein transport, while the topogenesis of mitochondrial outer membrane β-barrel (TOB)/sorting and assembly machinery (SAM) complex plays an important role in the assembly of outer membrane proteins (Pfanner et al, 2004; Neupert and Herrmann, 2007; Endo and Yamano, 2010)
CONCLUDING REMARKS Multiple lines of evidence suggest that, in metazoans, Miro is primarily involved in the Ca2+-dependent regulation of mitochondrial transport; in non-metazoans, Miro plays a primary role in the maintenance of mitochondrial morphology and homeostasis (Table 1)
Summary
Mitochondria are essential organelles for aerobic energy production and metabolism in eukaryotic cells They frequently undergo changes in morphology and intracellular distribution through fusion, fission, and cytoskeleton-dependent transport, presumably to sustain their functional homeostasis. The functions and dynamics of mitochondria are linked to evolutionarily conserved proteins localized to the mitochondrial outer membrane. The Miro protein is a mitochondrial outer membrane-localized GTPase that is highly conserved throughout eukaryotes. MOLECULAR STRUCTURE OF Miro GTPases Miro GTPase is anchored to the mitochondrial outer membrane by its C-terminal transmembrane domain, leaving its N-terminus exposed to the cytoplasm. A recent study of Miro in fruit flies showed that its C-terminal GTPase domain is most structurally similar to Rheb, a Ras subfamily member (Mazhab-Jafari et al, 2012; Klosowiak et al, 2013). The two conserved EF hands of Miro have been shown to bind Ca2+ (MacAskill et al, 2009; Koshiba et al, 2011) and the flanking regions of the EF hands are highly conserved among eukaryotes (Vlahou et al, 2011). Klosowiak et al (2013) showed that these regions contain non-canonical “hidden” EF hands (hEF hands 1 and 2) followed www.frontiersin.org
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