Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 62,719 bioRxiv papers from 278,291 authors.

MISTERMINATE Mechanistically Links Mitochondrial Dysfunction with Proteostasis Failure

By Zhihao Wu, Ishaq Tantray, Junghyun Lim, Songjie Chen, Yu Li, Zoe Davis, Cole Citron, Jason Dong, Suzanna Gispert, Georg Auburger, Onn Brandman, Xiaolin Bi, Michael Snyder, Bingwei Lu

Posted 19 Feb 2019
bioRxiv DOI: 10.1101/554634 (published DOI: 10.1016/j.molcel.2019.06.031)

Mitochondrial dysfunction and proteostasis failure frequently coexist as hallmarks of neurodegenerative disease. How these pathologies are related is not well understood. Here we describe a phenomenon termed MISTERMINATE (mitochondrial stress-induced translational termination impairment and protein carboxyl terminal extension), which mechanistically links mitochondrial dysfunction with proteostasis failure. We show that mitochondrial dysfunction impairs translational termination of nuclear-encoded mitochondrial mRNAs including complex-I 30kD subunit (C-I30) mRNA, occurring on mitochondrial surface in Drosophila and mammalian cells. Ribosomes stalled at the normal stop codon continue to add to the C-terminus of C-I30 certain amino acids non-coded by mRNA template. C-terminally-extended C-I30 is toxic when assembled into C-I and forms aggregates in the cytosol. Enhancing co-translational quality control prevents C-I30 C-terminal extension and rescues mitochondrial and neuromuscular degeneration in a Parkinson disease model. These findings emphasize the importance of efficient translation termination and reveal unexpected link between mitochondrial health and proteome homeostasis mediated by MISTERMINATE.

Download data

  • Downloaded 386 times
  • Download rankings, all-time:
    • Site-wide: 25,754 out of 62,719
    • In cell biology: 1,182 out of 2,987
  • Year to date:
    • Site-wide: 7,498 out of 62,719
  • Since beginning of last month:
    • Site-wide: 15,225 out of 62,719

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News