RT Journal Article
SR Electronic
T1 Metabolic regulation of misfolded protein import into mitochondria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.03.29.534670
DO 10.1101/2023.03.29.534670
A1 Yuhao Wang
A1 Linhao Ruan
A1 Jin Zhu
A1 Xi Zhang
A1 Alexander Chih-Chieh Chang
A1 Alexis Tomaszewski
A1 Rong Li
YR 2023
UL http://biorxiv.org/content/early/2023/03/29/2023.03.29.534670.abstract
AB Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the ‘mitochondria as guardian in cytosol’ (MAGIC) whereby cytosolic misfolded proteins are imported into and degraded inside mitochondria. In this study, a genome-wide screen in yeast uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of misfolded proteins into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by misfolded proteins such as those associated with neurodegenerative diseases.Competing Interest StatementThe authors have declared no competing interest.