RHOT1 GTPase cycle

Stable Identifier
R-HSA-9013425
Type
Pathway
Species
Homo sapiens
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This pathway catalogues guanine nucleotide exchange factors (GEFs) and effectors of RHOT1 (also known as MIRO-1). RHOT1 possesses a high intrinsic GTP-ase activity and does not require a GTPase activator protein (GAP) (Peters et al. 2018). No GDP dissociation inhibitors (GDIs) have been reported to interact with RHOT1. RHOT1 is a mitochondrial RHO GTPase. Like related RHOT2 (MIRO-2), RHOT1 localizes to the outer mitochondrial membrane. RHOT1 is implicated in mitochondrial movement inside the cells (Schwarz 2013), including the axonal transport of mitochondria in neurons (Saxton and Hollenbeck 2012; Birsa et al. 2013; Devine et al. 2016), as well as mitochondrial fission and fusion (Saxton and Hollenbeck 2012). RHOT1/RHOT2-mediated mitochondrial turnover is affected in neurodegenerative diseases (Birsa et al. 2013; Devine et al. 2016). RHOT1 can localize to peroxisomes and regulate peroxisome motility and fission (Castro et al. 2018, Okumoto et al. 2018, Covill-Cooke et al. 2020). RHOT1 is also involved in the regulation of ER-mitochondria membrane contact sites (Grossmann et al. 2019, Modi et al. 2019).
Upregulation of RHOT1 has a neuroprotective effect in ischemic stroke (Wei et al. 2019).

Literature References
PubMed ID Title Journal Year
22619228 The axonal transport of mitochondria

Saxton, WM, Hollenbeck, PJ

J. Cell. Sci. 2012
31303019 Mutations in RHOT1 Disrupt Endoplasmic Reticulum-Mitochondria Contact Sites Interfering with Calcium Homeostasis and Mitochondrial Dynamics in Parkinson's Disease

Grossmann, D, Berenguer-Escuder, C, Bellet, ME, Scheibner, D, Bohler, J, Massart, F, Rapaport, D, Skupin, A, Fouquier d'Hérouël, A, Sharma, M, Ghelfi, J, Raković, A, Lichtner, P, Antony, P, Glaab, E, May, P, Dimmer, KS, Fitzgerald, JC, Grünewald, A, Krüger, R

Antioxid Redox Signal 2019
24256248 Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins

Birsa, N, Norkett, R, Higgs, N, Lopez-Domenech, G, Kittler, JT

Biochem. Soc. Trans. 2013
31562315 Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery

Modi, S, Lopez-Domenech, G, Halff, EF, Covill-Cooke, C, Ivankovic, D, Melandri, D, Arancibia-Cárcamo, IL, Burden, JJ, Lowe, AR, Kittler, JT

Nat Commun 2019
23732472 Mitochondrial trafficking in neurons

Schwarz, TL

Cold Spring Harb Perspect Biol 2013
29364559 A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Castro, IG, Richards, DM, Metz, J, Costello, JL, Passmore, JB, Schrader, TA, Gouveia, A, Ribeiro, D, Schrader, M

Traffic 2018
31454517 Neuroprotection by mesenchymal stem cell (MSC) administration is enhanced by local cooling infusion (LCI) in ischemia

Wei, W, Wu, D, Duan, Y, Elkin, KB, Chandra, A, Guan, L, Peng, C, He, X, Wu, C, Ji, X, Ding, Y

Brain Res. 2019
31894645 Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2

Covill-Cooke, C, Toncheva, VS, Drew, J, Birsa, N, Lopez-Domenech, G, Kittler, JT

EMBO Rep 2020
30513825 Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism

Peters, DT, Kay, L, Eswaran, J, Lakey, JH, Soundararajan, M

Int J Mol Sci 2018
26707701 Miro sculpts mitochondrial dynamics in neuronal health and disease

Devine, MJ, Birsa, N, Kittler, JT

Neurobiol. Dis. 2016
29222186 New splicing variants of mitochondrial Rho GTPase-1 (Miro1) transport peroxisomes

Okumoto, K, Ono, T, Toyama, R, Shimomura, A, Nagata, A, Fujiki, Y

J Cell Biol 2018
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