Department of Molecular, Cell and Cancer Biology; Electron Microscopy Core; Department of Radiology
Amino Acids, Peptides, and Proteins | Cell and Developmental Biology | Cellular and Molecular Physiology | Molecular Biology
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 (UPR(mt)) 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 UPR(mt) 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 UPR(mt) activation.
Mitochondria, Energy metabolism, Caenorhabditis elegans, Chaperones
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DOI of Published Version
Shpilka T, Du Y, Yang Q, Melber A, Uma Naresh N, Lavelle J, Kim S, Liu P, Weidberg H, Li R, Yu J, Zhu LJ, Strittmatter L, Haynes CM. UPRmt scales mitochondrial network expansion with protein synthesis via mitochondrial import in Caenorhabditis elegans. Nat Commun. 2021 Jan 20;12(1):479. doi: 10.1038/s41467-020-20784-y. PMID: 33473112; PMCID: PMC7817664. Link to article on publisher's site
Shpilka T, Du Y, Yang Q, Melber A, Uma Naresh N, Lavelle J, Kim S, P, Weidberg H, Li R, Yu J, Zhu LJ, Strittmatter L, Haynes CM. (2021). UPR(mt) scales mitochondrial network expansion with protein synthesis via mitochondrial import in Caenorhabditis elegans. Radiology Publications. https://doi.org/10.1038/s41467-020-20784-y. Retrieved from https://escholarship.umassmed.edu/radiology_pubs/592
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This work is licensed under a Creative Commons Attribution 4.0 License.