TY - JOUR
T1 - Multitiered and cooperative surveillance of mitochondrial phosphatidylserine decarboxylase 1
AU - Ogunbona, Oluwaseun B.
AU - Onguka, Ouma
AU - Calzada, Elizabeth
AU - Claypool, Steven M.
N1 - Funding Information:
We thank Jeff Schatz and Carla Koehler for antibodies, Sin Urban (JHMI) for the suggestion that the serine of the LGST motif may be part of a catalytic triad, and Pingdewinde N. Sam and James O. Owusu (Department of Physiology, Johns Hopkins University School of Medicine) for technical assistance. This work was supported by a National Institutes of Health grant (R01GM111548) to S.M.C.; a Biochemistry, Cellular, and Molecular Biology Program training grant (T32GM007445) to O.O. and E.C.; and a predoctoral fellowship from the American Heart Association (15PRE24480066) to O.B.O. We declare no competing financial interests. O.B.O., O.O., and S.M.C. designed research; O.B.O., O.O., E.C., and S.M.C. performed research and analyzed data; and O.B.O., O.O., and S.M.C. wrote the paper.
Publisher Copyright:
© 2017 American Society for Microbiology.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
KW - Membrane biogenesis
KW - Membranes
KW - Phosphatidylethanolamine
KW - Phospholipids
KW - Quality control proteases
UR - http://www.scopus.com/inward/record.url?scp=85027382025&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85027382025&partnerID=8YFLogxK
U2 - 10.1128/MCB.00049-17
DO - 10.1128/MCB.00049-17
M3 - Article
C2 - 28606933
AN - SCOPUS:85027382025
SN - 0270-7306
VL - 37
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 17
M1 - e00049-17
ER -