@article{3da945d87ba646b49f8ca4ec7f116373,
title = "Yeast homologs of human MCUR1 regulate mitochondrial proline metabolism",
abstract = "Mitochondria house evolutionarily conserved pathways of carbon and nitrogen metabolism that drive cellular energy production. Mitochondrial bioenergetics is regulated by calcium uptake through the mitochondrial calcium uniporter (MCU), a multi-protein complex whose assembly in the inner mitochondrial membrane is facilitated by the scaffold factor MCUR1. Intriguingly, many fungi that lack MCU contain MCUR1 homologs, suggesting alternate functions. Herein, we characterize Saccharomyces cerevisiae homologs Put6 and Put7 of MCUR1 as regulators of mitochondrial proline metabolism. Put6 and Put7 are tethered to the inner mitochondrial membrane in a large hetero-oligomeric complex, whose abundance is regulated by proline. Loss of this complex perturbs mitochondrial proline homeostasis and cellular redox balance. Yeast cells lacking either Put6 or Put7 exhibit a pronounced defect in proline utilization, which can be corrected by the heterologous expression of human MCUR1. Our work uncovers an unexpected role of MCUR1 homologs in mitochondrial proline metabolism.",
author = "Mohammad Zulkifli and Neff, {John K.} and Timbalia, {Shrishiv A.} and Garza, {Natalie M.} and Yingqi Chen and Watrous, {Jeramie D.} and Marta Murgia and Trivedi, {Prachi P.} and Anderson, {Steven K.} and Dhanendra Tomar and Roland Nilsson and Muniswamy Madesh and Mohit Jain and Gohil, {Vishal M.}",
note = "Funding Information: We thank Dr. Jan Brix, for generously providing us with antibodies. We are grateful to Dr. Matthias Mann for his support in mass spectrometry data generation and analysis. We thank Microscopy and Imaging Center, Texas A&M University, for their assistance with confocal microscopy. We are grateful to Dr. Richard Gomer lab at Texas A&M University for helping with the flow cytometry data generation and analysis. We thank Dr. Craig Kaplan for providing yeast expression vectors. This work was supported by the Welch Foundation Grant (A-1810) and the National Institutes of Health awards R01GM111672 to V.M.G.; S10OD020025 and R01ES027595 to M.J.; K01DK116917 to J.D.W. Y.C. was supported by a UC San Diego Chancellor{\textquoteright}s Research Excellence Scholarship and R.N. was supported by the Foundation for Strategic Research grant no. FFL12-0220. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-18704-1",
language = "English (US)",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}