Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease.

Proc Natl Acad Sci U S A 2014 Sep 18;111(35):E3631-40. Epub 2014 Aug 18.

Departments of Biochemistry,

Defective mitochondrial distribution in neurons is proposed to cause ATP depletion and calcium-buffering deficiencies that compromise cell function. However, it is unclear whether aberrant mitochondrial motility and distribution alone are sufficient to cause neurological disease. Calcium-binding mitochondrial Rho (Miro) GTPases attach mitochondria to motor proteins for anterograde and retrograde transport in neurons. Using two new KO mouse models, we demonstrate that Miro1 is essential for development of cranial motor nuclei required for respiratory control and maintenance of upper motor neurons required for ambulation. Neuron-specific loss of Miro1 causes depletion of mitochondria from corticospinal tract axons and progressive neurological deficits mirroring human upper motor neuron disease. Although Miro1-deficient neurons exhibit defects in retrograde axonal mitochondrial transport, mitochondrial respiratory function continues. Moreover, Miro1 is not essential for calcium-mediated inhibition of mitochondrial movement or mitochondrial calcium buffering. Our findings indicate that defects in mitochondrial motility and distribution are sufficient to cause neurological disease.

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1402449111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156725PMC
September 2014
26 Reads

Publication Analysis

Top Keywords

mitochondrial
9
motility distribution
8
mitochondrial motility
8
distribution sufficient
8
miro1 essential
8
upper motor
8
neuron disease
8
neurological disease
8
sufficient neurological
8
mitochondrial movement
8
progressive neurological
4
proteins anterograde
4
neurological deficits
4
motor proteins
4
anterograde retrograde
4
axons progressive
4
neurons mouse
4
tract axons
4
transport neurons
4
retrograde transport
4

Similar Publications