Send to

Choose Destination
mBio. 2018 Feb 27;9(1). pii: e00084-18. doi: 10.1128/mBio.00084-18.

Mmf1p Couples Amino Acid Metabolism to Mitochondrial DNA Maintenance in Saccharomyces cerevisiae.

Author information

Department of Microbiology, University of Georgia, Athens, Georgia, USA.
Department of Microbiology, University of Georgia, Athens, Georgia, USA


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.IMPORTANCE Deleterious reactive metabolites are produced as a consequence of many intracellular biochemical transformations. Importantly, reactive metabolites that appear short-lived in vitro have the potential to persist within intracellular environments, leading to pervasive cell damage and diminished fitness. To overcome metabolite damage, organisms utilize enzymatic reactive-metabolite defense systems to rid the cell of deleterious metabolites. In this report, we describe the importance of the RidA/YER057c/UK114 enamine/imine deaminase family in preventing 2-aminoacrylate stress in yeast. Saccharomyces cerevisiae lacking the enamine/imine deaminase Mmf1p was shown to experience pleiotropic growth defects and fails to maintain its mitochondrial genome. Our results provide the first line of evidence that uncontrolled 2-aminoacrylate stress derived from mitochondrial serine metabolism can negatively impact mitochondrial DNA maintenance in eukaryotes.


2-aminoacrylate; RidA; enamine deaminase; metabolite stress; mitochondrial genome

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center