This report describes a Parkinson-like neurodegenerative disease model using the Drosophila Miro gene. Dmel\Miro is orthologous to two human genes, RHOT1 and RHOT2, which are mitochondrial Rho GTPases involved in mitochondrial homeostasis and trafficking. RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated for Miro.
Neither human gene (RHOT1, RHOT2) has been introduced into flies.
In the fly, Miro over-expression in dopaminergic neurons results in aberrant mitochondrial aggregation and dopaminergic neuron loss; this is very similar to the neural phenotype observed for Dmel\Pink1 mutations (see the human disease model report 'Parkinson disease 6'; FBhh0000009). Decreased levels of Miro, effected by RNAi, ameliorate the detrimental effects caused by the loss of Pink1. The role of Miro in regulating calcium (2+) homeostasis in dopaminergic neurons has been investigated, including in the context of Parkinson disease models (PD6, FBhh0000009; PD8, FBhh0000011).
[updated Jul. 2019 by FlyBase; FBrf0222196]
RHOT1 and RHOT2 encode mitochondrial GTPases involved in mitochondrial trafficking. [Gene Cards, RHOT1, RHOT2; 2019.07.17]
Mitochondrial Rho proteins (Miro-1 encoded by RHOT1 and Miro-2 encoded by RHOT2) are atypical Rho GTPases. They have a unique domain organization, with tandem GTP-binding domains and two EF hand domains, that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis. (HGNC Gene Group, https://www.genenames.org/data/genegroup/#!/group/392).
Many to one: 2 human to 1 Drosophila.
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of RHOT1 and RHOT2 (1 Drosophila to 2 human). Dmel\Miro shares 46-49% identity and 64-66% similarity with the human genes.
