Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae
A variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion....
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American Society for Microbiology
2018-02-01
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doaj-5a074630ac1a4c37a8cfe76162dc73f62021-07-02T15:48:00ZengAmerican Society for MicrobiologymBio2150-75112018-02-0191e00084-1810.1128/mBio.00084-18Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiaeDustin C. ErnstDiana M. DownsSusan GottesmanA variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion. 2-Aminoacrylate is a reactive enamine generated by pyridoxal 5′-phosphate-dependent α,β-eliminases as an obligatory intermediate in the breakdown of serine. In prokaryotes, members of the broadly conserved RidA family (PF14588) prevent metabolic stress by deaminating 2-aminoacrylate to pyruvate. Here, we demonstrate that unmanaged 2-aminoacrylate accumulation in Saccharomyces cerevisiae mitochondria causes transient metabolic stress and the irreversible loss of mitochondrial DNA. The RidA family protein Mmf1p deaminates 2-aminoacrylate, preempting metabolic stress and loss of the mitochondrial genome. Disruption of the mitochondrial pyridoxal 5′-phosphate-dependent serine dehydratases (Ilv1p and Cha1p) prevents 2-aminoacrylate formation, avoiding stress in the absence of Mmf1p. Furthermore, chelation of iron in the growth medium improves maintenance of the mitochondrial genome in yeast challenged with 2-aminoacrylate, suggesting that 2-aminoacrylate-dependent loss of mitochondrial DNA is influenced by disruption of iron homeostasis. Taken together, the data indicate that Mmf1p indirectly contributes to mitochondrial DNA maintenance by preventing 2-aminoacrylate stress derived from mitochondrial amino acid metabolism.http://mbio.asm.org/cgi/content/full/9/1/e00084-18 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dustin C. Ernst Diana M. Downs Susan Gottesman |
spellingShingle |
Dustin C. Ernst Diana M. Downs Susan Gottesman Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae mBio |
author_facet |
Dustin C. Ernst Diana M. Downs Susan Gottesman |
author_sort |
Dustin C. Ernst |
title |
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae |
title_short |
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae |
title_full |
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae |
title_fullStr |
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae |
title_full_unstemmed |
Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae |
title_sort |
mmf1p couples amino acid metabolism to mitochondrial dna maintenance in saccharomyces cerevisiae |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2018-02-01 |
description |
A variety of metabolic deficiencies and human diseases arise from the disruption of mitochondrial enzymes and/or loss of mitochondrial DNA. Mounting evidence shows that eukaryotes have conserved enzymes that prevent the accumulation of reactive metabolites that cause stress inside the mitochondrion. 2-Aminoacrylate is a reactive enamine generated by pyridoxal 5′-phosphate-dependent α,β-eliminases as an obligatory intermediate in the breakdown of serine. In prokaryotes, members of the broadly conserved RidA family (PF14588) prevent metabolic stress by deaminating 2-aminoacrylate to pyruvate. Here, we demonstrate that unmanaged 2-aminoacrylate accumulation in Saccharomyces cerevisiae mitochondria causes transient metabolic stress and the irreversible loss of mitochondrial DNA. The RidA family protein Mmf1p deaminates 2-aminoacrylate, preempting metabolic stress and loss of the mitochondrial genome. Disruption of the mitochondrial pyridoxal 5′-phosphate-dependent serine dehydratases (Ilv1p and Cha1p) prevents 2-aminoacrylate formation, avoiding stress in the absence of Mmf1p. Furthermore, chelation of iron in the growth medium improves maintenance of the mitochondrial genome in yeast challenged with 2-aminoacrylate, suggesting that 2-aminoacrylate-dependent loss of mitochondrial DNA is influenced by disruption of iron homeostasis. Taken together, the data indicate that Mmf1p indirectly contributes to mitochondrial DNA maintenance by preventing 2-aminoacrylate stress derived from mitochondrial amino acid metabolism. |
url |
http://mbio.asm.org/cgi/content/full/9/1/e00084-18 |
work_keys_str_mv |
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1721327009798291456 |