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  The metabolic growth limitations of petite cells lacking the mitochondrial genome

Vowinckel, J., Hartl, J., Marx, H., Kerick, M., Runggatscher, K., Keller, M. A., et al. (2021). The metabolic growth limitations of petite cells lacking the mitochondrial genome. Nature Metabolism, 3, 1521-1535. doi:10.1038/s42255-021-00477-6.

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Vowinckel , Jakob , Author
Hartl, Johannes , Author
Marx, Hans, Author
Kerick, Martin, Author
Runggatscher, Kathrin , Author
Keller, Markus A., Author
Mülleder, Michael , Author
Day, Jason, Author
Weber, Manuela , Author
Rinnerthaler, Mark , Author
Yu, Jason S. L. , Author
Kaur Aulakh, Simran, Author
Lehmann, Andrea , Author
Mattanovich, Diethard , Author
Timmermann, Bernd1, Author           
Zhang, Nianshu , Author
Dunn, Cory D. , Author
MacRae, James I. , Author
Breitenbach, Michael , Author
Ralser, Markus, Author
Affiliations:
1Sequencing Core Facility (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

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 Abstract: Eukaryotic cells can survive the loss of their mitochondrial genome, but consequently suffer from severe growth defects. ‘Petite yeasts’, characterized by mitochondrial genome loss, are instrumental for studying mitochondrial function and physiology. However, the molecular cause of their reduced growth rate remains an open question. Here we show that petite cells suffer from an insufficient capacity to synthesize glutamate, glutamine, leucine and arginine, negatively impacting their growth. Using a combination of molecular genetics and omics approaches, we demonstrate the evolution of fast growth overcomes these amino acid deficiencies, by alleviating a perturbation in mitochondrial iron metabolism and by restoring a defect in the mitochondrial tricarboxylic acid cycle, caused by aconitase inhibition. Our results hence explain the slow growth of mitochondrial genome-deficient cells with a partial auxotrophy in four amino acids that results from distorted iron metabolism and an inhibited tricarboxylic acid cycle.

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Language(s): eng - English
 Dates: 2021-09-102021-11-182021-11
 Publication Status: Published in print
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 Identifiers: DOI: 10.1038/s42255-021-00477-6
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Title: Nature Metabolism
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 3 Sequence Number: - Start / End Page: 1521 - 1535 Identifier: ISSN: 2522-5812
CoNE: https://pure.mpg.de/cone/journals/resource/2522-5812