# RHOT1

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Protein-coding gene in the species Homo sapiens

RHOT1 Identifiers Aliases RHOT1, ARHT1, MIRO-1, MIRO1, ras homolog family member T1 External IDs OMIM: 613888; MGI: 1926078; HomoloGene: 56803; GeneCards: RHOT1; OMA:RHOT1 - orthologs Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q11.2 Start 32,142,454 bp[1] End 32,253,374 bp[1] Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B5|11 47.62 cM Start 80,099,845 bp[2] End 80,158,733 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell Brodmann area 23 secondary oocyte visceral pleura primary visual cortex palpebral conjunctiva skin of thigh gingival epithelium parietal pleura sperm Top expressed in neural layer of retina secondary oocyte primary oocyte spermatocyte spermatid right ventricle zygote seminiferous tubule temporal muscle sternocleidomastoid muscle More reference expression data BioGPS More reference expression data Gene ontology Molecular function GTPase activity protein binding calcium ion binding hydrolase activity metal ion binding nucleotide binding GTP binding molecular function Cellular component integral component of membrane cytosol membrane plasma membrane mitochondrion integral component of mitochondrial outer membrane mitochondrial outer membrane Biological process cellular homeostasis regulation of small GTPase mediated signal transduction mitochondrial outer membrane permeabilization mitochondrion organization protein deubiquitination establishment of mitochondrion localization by microtubule attachment regulation of neurotransmitter secretion regulation of organelle transport along microtubule mitochondrion transport along microtubule Rho protein signal transduction regulation of mitochondrion organization Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 55288 59040 Ensembl ENSG00000126858 ENSMUSG00000017686 UniProt Q8IXI2 Q8BG51 RefSeq (mRNA) NM_001033566 NM_001033567 NM_001033568 NM_001288754 NM_001288755 NM_001288758 NM_018307 NM_001163354 NM_001163355 NM_021536 NM_001362868 NM_001362869 NM_001362870 RefSeq (protein) NP_001028738 NP_001028739 NP_001028740 NP_001275683 NP_001275684 NP_001275687 NP_060777 NP_001156826 NP_001156827 NP_067511 NP_001349797 NP_001349798 NP_001349799 NP_001391057 NP_001391058 Location (UCSC) Chr 17: 32.14 – 32.25 Mb Chr 11: 80.1 – 80.16 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**Mitochondrial Rho GTPase 1** (MIRO1) is an [enzyme](/source/Enzyme) that in humans is encoded by the *RHOT1* [gene](/source/Gene) on chromosome 17.[5][6] As a [Miro](/source/Miro_(protein)) protein [isoform](/source/Isoform), the protein facilitates mitochondrial transport by attaching the [mitochondria](/source/Mitochondria) to the motor/adaptor complex.[7] Through its key role in mitochondrial transport, RHOT1 is involved in mitochondrial [homeostasis](/source/Homeostasis) and [apoptosis](/source/Apoptosis), as well as [Parkinson's disease](/source/Parkinson's_disease) (PD) and [cancer](/source/Cancer).[7][8][9]

## Structure

In mammals, RHOT1 is one of two Miro isoforms. Both isoforms share a structure consisting of two EF-hand motifs linking two GTP-binding domains and a C-terminal transmembrane domain that attaches the protein to the [outer mitochondrial membrane](/source/Outer_mitochondrial_membrane) (OMM).[7][10] The EF-hand motifs serve as binding sites for the adaptor protein Milton and the [kinesin heavy chain](/source/KIF5B).[11] These domains can also bind calcium ions, and the binding results in a conformational change that dissociates the mitochondrial surface from kinesin.[7][10]

## Function

RHOT1 is a member of the [Rho GTPase family](/source/Rho_family_of_GTPases) and one of two isoforms of the protein Miro: RHOT1 (Miro1) and [RHOT2](/source/RHOT2) (Miro2).[7][11] Compared to the rest of the Rho GTPase family, the Miro isoforms are considered atypical due to their different regulation.[9] Moreover, the Miro isoforms are only expressed in the mitochondria.[12]

Miro associates with Milton ([TRAK1](/source/TRAK1)/[2](/source/TRAK2)) and the motor proteins [kinesin](/source/Kinesin) and [dynein](/source/Dynein) to form the mitochondrial motor/adaptor complex. Miro functions to tether the complex to the mitochondrion while the complex transports the mitochondrion via [microtubules](/source/Microtubule) within cells.[7][8] Though Miro has been predominantly studied in [neurons](/source/Neuron), the protein has also been observed to participate in the transport of mitochondria in [lymphocytes](/source/Lymphocyte) toward [inflamed](/source/Inflammation) endothelia.[11]

The motor/adaptor complex is regulated by calcium ion levels. At high concentrations, calcium ions arrest mitochondrial transport by binding Miro, causing the complex to detach from the organelle. Considering that physiological factors such as activation of [glutamate receptors](/source/Glutamate_receptor) in dendrites, [action potentials](/source/Action_potential) in axons, and neuromodulators may elevate calcium ion levels, this regulatory mechanism likely serves to keep mitochondria in such areas to provide calcium ion buffering and active export and, thus, maintain homeostasis.[7]

In addition, Miro regulates [mitochondrial fusion](/source/Mitochondrial_fusion) and [mitophagy](/source/Mitophagy) in conjunction with [mitofusin](https://en.wikipedia.org/w/index.php?title=Mitofusin&action=edit&redlink=1). According to one model, damaged mitochondria are sequestered from healthy mitochondria by the degradation of Miro and mitofusin. Miro degradation halts their movement while mitofusin degradation prevents them from fusing with healthy mitochondria, thus facilitating their clearance by autophagosomes.[7]

Though the exact mechanisms remain to be elucidated, RHOT1 has been implicated in promoting [caspase](/source/Caspase)-dependent apoptosis.[5]

## Clinical significance

Studies indicate that Miro may be involved in PD.[8] In neurons, Miro interacts with two key proteins involved in PD, PINK1 and Parkin.[7] Following depolarization of the mitochondria, PINK1 phosphorylates Miro at multiple sites, including S156, and Parkin ubiquitinates Miro, targeting it for proteasomal degradation.[7][8] Degradation of Miro then halts mitochondrial transport.[7]

Though the Rho GTPase family is closely associated with cancer progression, there are few studies demonstrating such association with the atypical Miro proteins. Nonetheless, RHOT1 has been implicated in pancreatic cancer as a tumor suppressor through its regulation of mitochondrial homeostasis and apoptosis. Thus, this protein could serve as a therapeutic target for cancer treatment.[9]

## Interactions

RHOT1 has been shown to [interact](/source/Protein-protein_interaction) with:

- [ALEX3](/source/ARMCX3),[7]

- [DISC1](/source/DISC1),[12]

- [Dynein](/source/Dynein),[7]

- [HUMMR](https://en.wikipedia.org/w/index.php?title=MGARP&action=edit&redlink=1),[7]

- [kinesin heavy chain](/source/Kinesin) (KHC),[7]

- Mitofusin ([MFN1](/source/MFN1)/[MFN2](/source/MFN2)),[7]

- Milton ([TRAK1](/source/TRAK1)/[TRAK2](/source/TRAK2)),[7]

- [Parkin](/source/Parkin_(ligase)),[7]

- [PINK1](/source/PINK1),[7] and

- [OGT](/source/OGT_(gene)).[7]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000126858](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000126858) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000017686](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000017686) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=55288). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=59040). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. ^ [***a***](#cite_ref-pmid12482879_5-0) [***b***](#cite_ref-pmid12482879_5-1) Fransson A, Ruusala A, Aspenström P (Feb 2003). ["Atypical Rho GTPases have roles in mitochondrial homeostasis and apoptosis"](https://doi.org/10.1074%2Fjbc.M208609200). *The Journal of Biological Chemistry*. **278** (8): 6495–502. [doi](/source/Doi_(identifier)):[10.1074/jbc.M208609200](https://doi.org/10.1074%2Fjbc.M208609200). [PMID](/source/PMID_(identifier)) [12482879](https://pubmed.ncbi.nlm.nih.gov/12482879).

1. **[^](#cite_ref-entrez_6-0)** ["Entrez Gene: RHOT1 ras homolog gene family, member T1"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=55288).

1. ^ [***a***](#cite_ref-pmid23732472_7-0) [***b***](#cite_ref-pmid23732472_7-1) [***c***](#cite_ref-pmid23732472_7-2) [***d***](#cite_ref-pmid23732472_7-3) [***e***](#cite_ref-pmid23732472_7-4) [***f***](#cite_ref-pmid23732472_7-5) [***g***](#cite_ref-pmid23732472_7-6) [***h***](#cite_ref-pmid23732472_7-7) [***i***](#cite_ref-pmid23732472_7-8) [***j***](#cite_ref-pmid23732472_7-9) [***k***](#cite_ref-pmid23732472_7-10) [***l***](#cite_ref-pmid23732472_7-11) [***m***](#cite_ref-pmid23732472_7-12) [***n***](#cite_ref-pmid23732472_7-13) [***o***](#cite_ref-pmid23732472_7-14) [***p***](#cite_ref-pmid23732472_7-15) [***q***](#cite_ref-pmid23732472_7-16) [***r***](#cite_ref-pmid23732472_7-17) [***s***](#cite_ref-pmid23732472_7-18) [***t***](#cite_ref-pmid23732472_7-19) Schwarz TL (Jun 2013). ["Mitochondrial trafficking in neurons"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660831). *Cold Spring Harbor Perspectives in Biology*. **5** (6) a011304. [doi](/source/Doi_(identifier)):[10.1101/cshperspect.a011304](https://doi.org/10.1101%2Fcshperspect.a011304). [PMC](/source/PMC_(identifier)) [3660831](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660831). [PMID](/source/PMID_(identifier)) [23732472](https://pubmed.ncbi.nlm.nih.gov/23732472).

1. ^ [***a***](#cite_ref-pmid25761903_8-0) [***b***](#cite_ref-pmid25761903_8-1) [***c***](#cite_ref-pmid25761903_8-2) [***d***](#cite_ref-pmid25761903_8-3) van der Merwe C, Jalali Sefid Dashti Z, Christoffels A, Loos B, Bardien S (May 2015). "Evidence for a common biological pathway linking three Parkinson's disease-causing genes: parkin, PINK1 and DJ-1". *The European Journal of Neuroscience*. **41** (9): 1113–25. [doi](/source/Doi_(identifier)):[10.1111/ejn.12872](https://doi.org/10.1111%2Fejn.12872). [PMID](/source/PMID_(identifier)) [25761903](https://pubmed.ncbi.nlm.nih.gov/25761903). [S2CID](/source/S2CID_(identifier)) [24099106](https://api.semanticscholar.org/CorpusID:24099106).

1. ^ [***a***](#cite_ref-pmid22860091_9-0) [***b***](#cite_ref-pmid22860091_9-1) [***c***](#cite_ref-pmid22860091_9-2) Jiang H, He C, Geng S, Sheng H, Shen X, Zhang X, Li H, Zhu S, Chen X, Yang C, Gao H (2012). ["RhoT1 and Smad4 are correlated with lymph node metastasis and overall survival in pancreatic cancer"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409151). *PLOS ONE*. **7** (7) e42234. [Bibcode](/source/Bibcode_(identifier)):[2012PLoSO...742234J](https://ui.adsabs.harvard.edu/abs/2012PLoSO...742234J). [doi](/source/Doi_(identifier)):[10.1371/journal.pone.0042234](https://doi.org/10.1371%2Fjournal.pone.0042234). [PMC](/source/PMC_(identifier)) [3409151](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409151). [PMID](/source/PMID_(identifier)) [22860091](https://pubmed.ncbi.nlm.nih.gov/22860091).

1. ^ [***a***](#cite_ref-pmid16630562_10-0) [***b***](#cite_ref-pmid16630562_10-1) Fransson S, Ruusala A, Aspenström P (Jun 2006). "The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking". *Biochemical and Biophysical Research Communications*. **344** (2): 500–10. [Bibcode](/source/Bibcode_(identifier)):[2006BBRC..344..500F](https://ui.adsabs.harvard.edu/abs/2006BBRC..344..500F). [doi](/source/Doi_(identifier)):[10.1016/j.bbrc.2006.03.163](https://doi.org/10.1016%2Fj.bbrc.2006.03.163). [PMID](/source/PMID_(identifier)) [16630562](https://pubmed.ncbi.nlm.nih.gov/16630562).

1. ^ [***a***](#cite_ref-pmid24492963_11-0) [***b***](#cite_ref-pmid24492963_11-1) [***c***](#cite_ref-pmid24492963_11-2) Morlino G, Barreiro O, Baixauli F, Robles-Valero J, González-Granado JM, Villa-Bellosta R, Cuenca J, Sánchez-Sorzano CO, Veiga E, Martín-Cófreces NB, Sánchez-Madrid F (Apr 2014). ["Miro-1 links mitochondria and microtubule Dynein motors to control lymphocyte migration and polarity"](https://repositorio.uam.es/bitstream/10486/664660/1/links_morino_MCB_2014.pdf) (PDF). *Molecular and Cellular Biology*. **34** (8): 1412–26. [doi](/source/Doi_(identifier)):[10.1128/MCB.01177-13](https://doi.org/10.1128%2FMCB.01177-13). [PMC](/source/PMC_(identifier)) [3993592](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993592). [PMID](/source/PMID_(identifier)) [24492963](https://pubmed.ncbi.nlm.nih.gov/24492963).

1. ^ [***a***](#cite_ref-pmid24092329_12-0) [***b***](#cite_ref-pmid24092329_12-1) Ogawa F, Malavasi EL, Crummie DK, Eykelenboom JE, Soares DC, Mackie S, Porteous DJ, Millar JK (Feb 2014). ["DISC1 complexes with TRAK1 and Miro1 to modulate anterograde axonal mitochondrial trafficking"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900104). *Human Molecular Genetics*. **23** (4): 906–19. [doi](/source/Doi_(identifier)):[10.1093/hmg/ddt485](https://doi.org/10.1093%2Fhmg%2Fddt485). [PMC](/source/PMC_(identifier)) [3900104](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900104). [PMID](/source/PMID_(identifier)) [24092329](https://pubmed.ncbi.nlm.nih.gov/24092329).

## Further reading

- Hartley JL, Temple GF, Brasch MA (Nov 2000). ["DNA cloning using in vitro site-specific recombination"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC310948). *Genome Research*. **10** (11): 1788–95. [doi](/source/Doi_(identifier)):[10.1101/gr.143000](https://doi.org/10.1101%2Fgr.143000). [PMC](/source/PMC_(identifier)) [310948](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC310948). [PMID](/source/PMID_(identifier)) [11076863](https://pubmed.ncbi.nlm.nih.gov/11076863).

- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). ["Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC311072). *Genome Research*. **11** (3): 422–35. [doi](/source/Doi_(identifier)):[10.1101/gr.GR1547R](https://doi.org/10.1101%2Fgr.GR1547R). [PMC](/source/PMC_(identifier)) [311072](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC311072). [PMID](/source/PMID_(identifier)) [11230166](https://pubmed.ncbi.nlm.nih.gov/11230166).

- Aspenström P, Fransson A, Saras J (Jan 2004). ["Rho GTPases have diverse effects on the organization of the actin filament system"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223866). *The Biochemical Journal*. **377** (Pt 2): 327–37. [doi](/source/Doi_(identifier)):[10.1042/BJ20031041](https://doi.org/10.1042%2FBJ20031041). [PMC](/source/PMC_(identifier)) [1223866](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1223866). [PMID](/source/PMID_(identifier)) [14521508](https://pubmed.ncbi.nlm.nih.gov/14521508).

- Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW (Jun 2004). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". *Nature Biotechnology*. **22** (6): 707–16. [doi](/source/Doi_(identifier)):[10.1038/nbt971](https://doi.org/10.1038%2Fnbt971). [PMID](/source/PMID_(identifier)) [15146197](https://pubmed.ncbi.nlm.nih.gov/15146197). [S2CID](/source/S2CID_(identifier)) [27764390](https://api.semanticscholar.org/CorpusID:27764390).

- Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). ["From ORFeome to biology: a functional genomics pipeline"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC528930). *Genome Research*. **14** (10B): 2136–44. [doi](/source/Doi_(identifier)):[10.1101/gr.2576704](https://doi.org/10.1101%2Fgr.2576704). [PMC](/source/PMC_(identifier)) [528930](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC528930). [PMID](/source/PMID_(identifier)) [15489336](https://pubmed.ncbi.nlm.nih.gov/15489336).

- Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). ["The LIFEdb database in 2006"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347501). *Nucleic Acids Research*. **34** (Database issue): D415-8. [doi](/source/Doi_(identifier)):[10.1093/nar/gkj139](https://doi.org/10.1093%2Fnar%2Fgkj139). [PMC](/source/PMC_(identifier)) [1347501](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1347501). [PMID](/source/PMID_(identifier)) [16381901](https://pubmed.ncbi.nlm.nih.gov/16381901).

- Fransson S, Ruusala A, Aspenström P (Jun 2006). "The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking". *Biochemical and Biophysical Research Communications*. **344** (2): 500–10. [Bibcode](/source/Bibcode_(identifier)):[2006BBRC..344..500F](https://ui.adsabs.harvard.edu/abs/2006BBRC..344..500F). [doi](/source/Doi_(identifier)):[10.1016/j.bbrc.2006.03.163](https://doi.org/10.1016%2Fj.bbrc.2006.03.163). [PMID](/source/PMID_(identifier)) [16630562](https://pubmed.ncbi.nlm.nih.gov/16630562).

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Adapted from the Wikipedia article [RHOT1](https://en.wikipedia.org/wiki/RHOT1) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/RHOT1?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.