Mitochondrial Rho GTPase 2 (RHOT2) (RHOT2)

Mitochondrial Rho GTPase 2 (RHOT2), also known as MIRO2, is a specialized GTPase anchored to the outer mitochondrial membrane that plays a critical role in mitochondrial trafficking and distribution within cells (UniProt Q8IXI1). It functions as a key component of the Miro-Milton-Kinesin complex, which facilitates the microtubule-based transport of mitochondria, particularly in high-energy demanding cells like neurons (PubMed: 21183601). RHOT2 contains two GTPase domains and two calcium-binding EF-hand motifs, allowing it to regulate mitochondrial motility in response to intracellular calcium fluctuations (PubMed: 16203866). In the context of disease, RHOT2 is a substrate for the PINK1/Parkin pathway; its degradation is a prerequisite for mitophagy, and defects in this process are linked to the pathogenesis of Parkinson's disease (PubMed: 21525243). Furthermore, RHOT2 overexpression has been implicated in promoting the migration and invasion of various cancer cells by repositioning mitochondria to the leading edge of the cell (PubMed: 30104348). While there are currently no FDA-approved drugs specifically targeting RHOT2, it is considered an emerging therapeutic target for neurodegenerative disorders and metastatic cancers (PubMed: 31434769).

Other names

MIRO2Ras homolog family member T2Miro-2ARHT2C16orf39

Modulation of mitochondrial motility and distribution through the Miro-Milton-Kinesin complex (PubMed: 21183601).