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- Title
Metabolic regulation of misfolded protein import into mitochondria.
- Authors
Yuhao Wang; Linhao Ruan; Jin Zhu; Xi Zhang; Chih-Chieh Chang, Alexander; Tomaszewski, Alexis; Rong Li
- Abstract
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 (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs 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 MPs such as those associated with neurodegenerative diseases.
- Subjects
METABOLIC regulation; MITOCHONDRIAL proteins; TRANSCRIPTION factors; PLANT mitochondria; PROTEIN kinases; AMP-activated protein kinases; MITOCHONDRIAL membranes
- Publication
eLife, 2024, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.87518