Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration

Abstract

The ratio of ATP:ADP is highest at perinuclear sites, where mitochondria are dense, and dissipates toward the periphery. Miro1 positions mitochondria toward the cortical cytoskeleton. Deletion of Miro1 results in perinuclear clustering of mitochondria, altering intracellular ATP:ADP gradients, and impairs energy-expensive cell migratory processes.

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

“…Loss of MIRO1‐directed mitochondrial movement and distribution result in neurological defects 26. MIRO1‐mediated mitochondrial positioning is also suggested to shape intracellular energy gradients required for cell migration 29. We show that MIRO1 localises to peroxisomes and mitochondria, and alters peroxisome distribution and motility.…”

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

“…14 that positioning of mitochondria influences the shape of energy gradients in living mouse embryonic fibroblasts (MEFs). 16 Preventing accumulation of cortical mitochondria in Miro1 −/− MEFs led to reduced ATP/ADP ratios at the cell periphery and impaired actin dynamics, lamellipodia protrusion, and membrane ruffling. Furthermore, Miro1 −/− MEFs showed slower migration than WT MEFs.…”

“…These cortical mitochondria might support enhanced cell motility and invasion by numerous mechanisms (Figure ), including providing a local source of energy (ATP and guanosine triphosphate [GTP]) to fuel signal transduction and cytoskeleton dynamics at the leading edge. For instance, it was shown that positioning of mitochondria influences the shape of energy gradients in living mouse embryonic fibroblasts (MEFs) . Preventing accumulation of cortical mitochondria in Miro1 −/− MEFs led to reduced ATP/ADP ratios at the cell periphery and impaired actin dynamics, lamellipodia protrusion, and membrane ruffling.…”

Mitochondrial-cytoskeletal interactions: dynamic associations that facilitate network function and remodeling

“…Schuler et al [26] used 3D fluorescence spinning disc confocal and lattice light sheet microscopy to monitor the intracellular response of the biosensor Perceval HR, which provides a ratiometric measure of ATP/ADP levels. In wild type MEFs, a gradient was observed with highest ATP:ADP ratios in the perinuclear region and a gradual decline in the ratio toward the cell periphery.…”