A mitochondrial ribosomal and RNA decay pathway blocks cell proliferation

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Abstract

Proliferating cells require coordinated gene expression between the nucleus and mitochondria in order to divide, ensuring sufficient organelle number in daughter cells [1]. However, the machinery and mechanisms whereby proliferating cells monitor mitochondria and coordinate organelle biosynthesis remain poorly understood. Antibiotics inhibiting mitochondrial translation have emerged as therapeutics for human cancers because they block cell proliferation [2, 3]. These proliferative defects were attributable to modest decreases in mitochondrial respiration [3, 4], even though tumors are mainly glycolytic [5] and mitochondrial respiratory chain function appears to play a minor role in cell proliferation in vivo [6]. Here we challenge this interpretation by demonstrating that one class of antiproliferative antibiotic induces stalled mitochondrial ribosomes, which triggers a mitochondrial ribosome and RNA decay pathway. Rescue of the stalled mitochondrial ribosomes initiates a retrograde signaling response to block cell proliferation and occurs prior to any loss of mitochondrial respiration. The loss of respiratory chain function is simply a downstream effect of impaired mitochondrial translation and not the antiproliferative signal. This mitochondrial ribosome quality-control pathway is actively monitored in cells and constitutes an important organelle checkpoint for cell division. © 2013 Elsevier Ltd.

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Richter, U., Lahtinen, T., Marttinen, P., Myöhänen, M., Greco, D., Cannino, G., … Battersby, B. J. (2013). A mitochondrial ribosomal and RNA decay pathway blocks cell proliferation. Current Biology, 23(6), 535–541. https://doi.org/10.1016/j.cub.2013.02.019

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