Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis
Natalie M. Niemi,
Gary M. Wilson,
Katherine A. Overmyer,
Danielle C Lohman,
Kathryn L Schueler,
Alan D. Attie,
Joshua J. Coon,
David J. Pagliarini
Posted 25 Sep 2018
bioRxiv DOI: 10.1101/426247 (published DOI: 10.1038/s41467-019-11047-6)
Posted 25 Sep 2018
Mitochondrial proteins are replete with phosphorylation; however, the origin, abundance, and functional relevance of these modifications are largely unclear. Nonetheless, mitochondria possess multiple resident phosphatases, suggesting that protein dephosphorylation may be broadly important for mitochondrial activities. To explore this, we deleted the poorly characterized matrix phosphatase Pptc7 from mice using CRISPR-Cas9 technology. Strikingly, Pptc7-/- mice exhibited marked hypoketotic hypoglycemia, elevated acylcarnitines, and lactic acidosis, and died soon after birth. Pptc7-/- tissues had significantly diminished mitochondrial size and protein content despite normal transcript levels, but consistently elevated phosphorylation on select mitochondrial proteins. These putative Pptc7 substrates include the protein translocase complex subunit Timm50, whose phosphorylation reduced import activity. We further find that phosphorylation in or near the mitochondrial targeting sequences of multiple proteins can disrupt their import rates and matrix processing. Overall, our data define Pptc7 as a protein phosphatase essential for proper mitochondrial function and biogenesis during the extrauterine transition.
- Downloaded 428 times
- Download rankings, all-time:
- Site-wide: 37,236 out of 88,456
- In biochemistry: 1,063 out of 2,952
- Year to date:
- Site-wide: 66,316 out of 88,456
- Since beginning of last month:
- Site-wide: 54,314 out of 88,456
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!