A nuclear-based quality control pathway for non-imported mitochondrial proteins.
A nuclear-based quality control pathway for non-imported mitochondrial proteins.
复制标题
DOI：
10.7554/elife.61230
复制
发表时间：
2021-03-18
期刊：
影响因子：
7.7
通讯作者：
Hughes AL
中科院分区：
文献类型：
--
作者：
Shakya VP;Barbeau WA;Xiao T;Knutson CS;Schuler MH;Hughes AL
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 Saccharomyces 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 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.
