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The metabolic growth limitations of petite cells lacking the mitochondrial genome
File(s)
Author(s)
Vowinckel, Jakob
Hartl, Johannes
Marx, Hans
Kerick, Martin
Runggatscher, Kathrin
Type
Journal Article
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.
Date Issued
2021-11-18
Date Acceptance
2021-09-10
Citation
Nature Metabolism, 2021, 3 (11), pp.1521-1535
URI
URL
DOI
ISSN
2522-5812
Publisher
Nature Research
Start Page
1521
End Page
1535
Journal / Book Title
Nature Metabolism
Volume
3
Issue
11
Copyright Statement
© 2021, The Author(s), under exclusive licence to Springer Nature Limited. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1038/s42255-021-00477-6
Subjects
Mitochondria
Yeasts
Amino Acids
Fungal Proteins
Biomass
Cell Proliferation
Structure-Activity Relationship
Citric Acid Cycle
Energy Metabolism
Phenotype
Mutation
Membrane Potential, Mitochondrial
Genome, Mitochondrial
Publication Status
Published