Emerging roles for Mitochondrial Rho GTPases in tumor biology

Abstract

Mitochondrial Rho GTPases (MIRO1 and MIRO2) are primarily studied for their role as resident mitochondrial anchor proteins that facilitate mitochondria trafficking in neurons. However, it is now appreciated that these proteins have critical roles in cancer. In this review, we focus on examining the role of MIROs in cancer, including expression changes in tumors and the molecular mechanisms by which MIROs impact tumor cell growth, invasion, and metastasis. Additionally, we give an overview of how MIRO's functions in normal cells within the tumor microenvironment can support or inhibit tumor growth and metastasis. Although this is still an emerging field, the current consensus is that the MIROs primarily promote tumor progression of disparate tumor types. As mitochondrial proteins are now being targeted in the clinic, we discuss their potential as novel proteins to target in cancer.

Keywords: MIRO1; MIRO2; cancer; metastasis; mitochondria.

Figure 1

Overlapping and unique molecular functions of MIROs. An overview of the many different overlapping and nonoverlapping functions of the MIROs. MIRO, mitochondrial Rho GTPase.

Figure 2

Functions of MIRO1, circMIRO1, and MIRO2 in different tumors and tissues. An overview of the reported functions of MIROs in disparate tumor types. AAS, amino acid starvation; HCC, hepatocellular carcinoma; MIRO, mitochondrial Rho GTPase; TNT, tunneling nanotubes; SNPH, Syntaphilin. Created in BioRender.com.