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Beschreibung

Mitochondrial Rho GTPase (UniProt: A1L1L6, also known as Miro1) is encoded by the Rhot1 (also known as Rnf135, rCG34120) gene (Gene ID: 303351) in rat. Miro1 is a single-pass type IV membrane protein with a transmembrane domain (aa 605-627). It functions as a mitochondrial GTPase and is involved in mitochondrial trafficking and is considered to be a potential adaptor for microtubule?based peroxisome motility in mammalian cells. It plays a key role in mitochondrial motility on microtubules and in homeostasis. In mammals, Miro1 and Miro2 share about 60% sequence homology. Three acetylation sites for Miro1 have been identified in rat that are located on lysines 105, 525, and 629. Acetylation of Miro1 on lysine 105 (K105) is shown to increase mitochondrial transport and axon growth. Exposure of neurons to myelin-associated glycoprotein (MAG) and chondroitin sulfate proteoglycans reduces K105 acetylation of Miro1, which reduces axonal mitochondrial transport. Ac-Miro1 undergoes deacetylation with histone deacetylase 6 (HDAC6) and inhibition of HDAC6 increases Miro1 acetylation in axons. Loss of Miro1 in neurons causes depletion of mitochondria from corticospinal tract axons and leads to progressive neurological deficits similar to upper motor neuron disease. (Ref.: Kalinkski, AL., et al. (2019). J. Cell Biol. 218(6), 1871-1890, Castro, IG., et al. (2018). Traffic. 19(3), 229-242, Nguyen, TT., et al. (2014). Proc. Natl. Acad. Sci. USA. 111(35), E3631-E3640).