Multitiered and cooperative surveillance of mitochondrial phosphatidylserine decarboxylase 1

Oluwaseun B. Ogunbona, Ouma Onguka, Elizabeth Calzada, Steven M Claypool

Research output: Contribution to journalArticle

Abstract

Phosphatidylserine decarboxylase 1 (Psd1p), an ancient enzyme that converts phosphatidylserine to phosphatidylethanolamine in the inner mitochondrial membrane, must undergo an autocatalytic self-processing event to gain activity. Autocatalysis severs the protein into a large membrane-anchored β subunit that noncovalently associates with the small α subunit on the intermembrane space side of the inner membrane. Here, we determined that a temperature sensitive (ts) PSD1 allele is autocatalytically impaired and that its fidelity is closely monitored throughout its life cycle by multiple mitochondrial quality control proteases. Interestingly, the proteases involved in resolving misfolded Psd1ts vary depending on its autocatalytic status. Specifically, the degradation of a Psd1ts precursor unable to undergo autocatalysis requires the unprecedented cooperative and sequential actions of two inner membrane proteases, Oma1p and Yme1p. In contrast, upon heat exposure postautocatalysis, Psd1ts β subunits accumulate in protein aggregates that are resolved by Yme1p acting alone, while the released α subunit is degraded in parallel by an unidentified protease. Importantly, the stability of endogenous Psd1p is also influenced by Yme1p. We conclude that Psd1p, the key enzyme required for the mitochondrial pathway of phosphatidylethanolamine production, is closely monitored at several levels and by multiple mitochondrial quality control mechanisms present in the intermembrane space.

Original languageEnglish (US)
Article numbere00049-17
JournalMolecular and Cellular Biology
Volume37
Issue number17
DOIs
StatePublished - Sep 1 2017

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Peptide Hydrolases
Quality Control
Membranes
Phosphatidylserines
Mitochondrial Membranes
Enzymes
Life Cycle Stages
Hot Temperature
Alleles
Temperature
phosphatidylserine decarboxylase
Proteins
phosphatidylethanolamine

Keywords

  • Membrane biogenesis
  • Membranes
  • Phosphatidylethanolamine
  • Phospholipids
  • Quality control proteases

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Multitiered and cooperative surveillance of mitochondrial phosphatidylserine decarboxylase 1. / Ogunbona, Oluwaseun B.; Onguka, Ouma; Calzada, Elizabeth; Claypool, Steven M.

In: Molecular and Cellular Biology, Vol. 37, No. 17, e00049-17, 01.09.2017.

Research output: Contribution to journalArticle

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