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

Tammy T. Nguyen, Sang S. Oh, David Weaver, Agnieszka Lewandowska, Dane Maxfield, Max Hinderk Schuler, Nathan K. Smith, Jane Macfarlane, Gerald Saunders, Cheryl A. Palmer, Valentina Debattisti, Takumi Koshiba, Stefan Pulst, Eva L. Feldman, György Hajnóczky, Janet M. Shaw

研究成果: Contribution to journalArticle査読

106 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)E3631-E3640
ジャーナルProceedings of the National Academy of Sciences of the United States of America
111
35
DOI
出版ステータス出版済み - 9 2 2014

All Science Journal Classification (ASJC) codes

  • General

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