Projects per year
Abstract
Translation fidelity is crucial for prokaryotes and eukaryotic nuclear-encoded proteins; however, little is known about the role of mistranslation in mitochondria and its potential effects on metabolism. We generated yeast and mouse models with error-prone and hyper-accurate mitochondrial translation, and found that translation rate is more important than translational accuracy for cell function in mammals. Specifically, we found that mitochondrial mistranslation causes reduced overall mitochondrial translation and respiratory complex assembly rates. In mammals, this effect is compensated for by increased mitochondrial protein stability and upregulation of the citric acid cycle. Moreover, this induced mitochondrial stress signaling, which enables the recovery of mitochondrial translation via mitochondrial biogenesis, telomerase expression, and cell proliferation, and thereby normalizes metabolism. Conversely, we show that increased fidelity of mitochondrial translation reduces the rate of protein synthesis without eliciting a mitochondrial stress response. Consequently, the rate of translation cannot be recovered and this leads to dilated cardiomyopathy in mice. In summary, our findings reveal mammalian-specific signaling pathways that respond to changes in the fidelity of mitochondrial protein synthesis and affect metabolism.
Original language | English |
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Article number | e102155 |
Number of pages | 19 |
Journal | The EMBO Journal |
Volume | 38 |
Issue number | 24 |
DOIs | |
Publication status | Published - 16 Dec 2019 |
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Dive into the research topics of 'Stress signaling and cellular proliferation reverse the effects of mitochondrial mistranslation'. Together they form a unique fingerprint.Projects
- 1 Finished
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The role of non-coding RNAs in prostate cancer
Filipovska, A. (Investigator 01) & Rackham, O. (Investigator 02)
NHMRC National Health and Medical Research Council
1/01/19 → 31/12/22
Project: Research
Research output
- 25 Citations
- 1 Doctoral Thesis
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Regulation of Cytosolic and Mitochondrial Protein Synthesis in Health and Disease
Hughes, L., 2021, (Unpublished)Research output: Thesis › Doctoral Thesis
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