A nuclear-based quality control pathway for non-imported mitochondrial proteins
- University of Utah School of Medicine, United States
Abstract
Mitochondrial import deficiency causes cellular toxicity due to the accumulation of non-imported mitochondrial precursor proteins, termed mitoprotein-induced stress. Despite the burden mis-localized mitochondrial precursors place on cells, our understanding of the systems that dispose of these proteins is incomplete. Here, we cataloged the location and steady-state abundance of mitochondrial precursor proteins during mitochondrial impairment in S. cerevisiae. We found that a number of non-imported mitochondrial proteins localize to the nucleus, where they are subjected to proteasome-dependent degradation through a process we term nuclear-associated mitoprotein degradation (mitoNUC). Recognition and destruction of mitochondrial precursors by the mitoNUC pathway requires the presence of an N-terminal mitochondrial targeting sequence (MTS) and is mediated by combined action of the E3 ubiquitin ligases San1, Ubr1, and Doa10. Impaired breakdown of precursors leads to alternative sequestration in nuclear-associated foci. These results identify the nucleus as an important destination for the disposal of non-imported mitochondrial precursors.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Viplendra PS Shakya
Funding
National Institute on Aging (AG043095)
- Adam L Hughes
National Institute of General Medical Sciences (GM119694)
- Adam L Hughes
American Federation for Aging Research
- Adam L Hughes
United Mitochondrial Disease Foundation
- Adam L Hughes
Kinship Foundation
- Adam L Hughes
Glenn Foundation for Medical Research
- Adam L Hughes
American Heart Association
- Max H Schuler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Shakya et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A nuclear-based quality control pathway for non-imported mitochondrial proteins
eLife 10:e61230.
https://doi.org/10.7554/eLife.61230
