Reactome | RHOT1 GTPase cycle

RHOT1 GTPase cycle

Stable Identifier

R-HSA-9013425

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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
31303019	Mutations in RHOT1 Disrupt Endoplasmic Reticulum-Mitochondria Contact Sites Interfering with Calcium Homeostasis and Mitochondrial Dynamics in Parkinson's Disease Rapaport, D, Massart, F, Sharma, M, Glaab, E, May, P, Grünewald, A, Fitzgerald, JC, Fouquier d'Hérouël, A, Raković, A, Antony, P, Scheibner, D, Berenguer-Escuder, C, Krüger, R, Skupin, A, Dimmer, KS, Grossmann, D, Ghelfi, J, Bohler, J, Bellet, ME, Lichtner, P	Antioxid Redox Signal	2019
22619228	The axonal transport of mitochondria Saxton, WM, Hollenbeck, PJ	J. Cell. Sci.	2012
24256248	Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins Norkett, R, Higgs, N, Lopez-Domenech, G, Birsa, N, Kittler, JT	Biochem. Soc. Trans.	2013
31562315	Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery Melandri, D, Covill-Cooke, C, Burden, JJ, Lowe, AR, Arancibia-Cárcamo, IL, Lopez-Domenech, G, Modi, S, Ivankovic, D, Kittler, JT, Halff, EF	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 Schrader, TA, Schrader, M, Metz, J, Passmore, JB, Ribeiro, D, Costello, JL, Castro, IG, Richards, DM, Gouveia, A	Traffic	2018
31454517	Neuroprotection by mesenchymal stem cell (MSC) administration is enhanced by local cooling infusion (LCI) in ischemia Wei, W, Ding, Y, Wu, D, Guan, L, Chandra, A, Duan, Y, Wu, C, Elkin, KB, Peng, C, Ji, X, He, X	Brain Res.	2019
31894645	Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2 Covill-Cooke, C, Lopez-Domenech, G, Birsa, N, Kittler, JT, Toncheva, VS, Drew, J	EMBO Rep	2020
30513825	Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism Lakey, JH, Kay, L, Soundararajan, M, Eswaran, J, Peters, DT	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, Nagata, A, Toyama, R, Ono, T, Shimomura, A, Fujiki, Y	J Cell Biol	2018