UPRmt scales mitochondrial network expansion with protein synthesis via mitochondrial import in Caenorhabditis elegans
Open Access
- 20 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-11
- https://doi.org/10.1038/s41467-020-20784-y
Abstract
As organisms develop, individual cells generate mitochondria to fulfill physiological requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS). Here, using the model organism Caenorhabditis elegans we demonstrate that ATFS-1 mediates an adaptable mitochondrial network expansion program that is active throughout normal development. Mitochondrial network expansion requires the relatively inefficient MTS in ATFS-1, which allows the transcription factor to be responsive to parameters that impact protein import capacity of the mitochondrial network. Increasing the strength of the ATFS-1 MTS impairs UPRmt activity by increasing accumulation within mitochondria. Manipulations of TORC1 activity increase or decrease ATFS-1 activity in a manner that correlates with protein synthesis. Lastly, expression of mitochondrial-targeted GFP is sufficient to expand the muscle cell mitochondrial network in an ATFS-1-dependent manner. We propose that mitochondrial network expansion during development is an emergent property of the synthesis of highly expressed mitochondrial proteins that exclude ATFS-1 from mitochondrial import, causing UPRmt activation. The mitochondrial network expands to accommodate cell growth, but how scaling occurs is unclear. Here, the authors show in C. elegans that ATFS-1 mitochondrial import is reduced when mitochondrial proteins are highly expressed, activating the unfolded protein response and causing expansion.This publication has 50 references indexed in Scilit:
- The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathwayProceedings of the National Academy of Sciences of the United States of America, 2013
- Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targetsGenome Research, 2012
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREBNature, 2011
- The Cell-Non-Autonomous Nature of Electron Transport Chain-Mediated LongevityCell, 2011
- Manipulation of FASTQ data with GalaxyBioinformatics, 2010
- The Matrix Peptide Exporter HAF-1 Signals a Mitochondrial UPR by Activating the Transcription Factor ZC376.7 in C. elegansMolecular Cell, 2010
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- Parkin is recruited selectively to impaired mitochondria and promotes their autophagyThe Journal of cell biology, 2008
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005