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Lipase Maturation Factor 1 Affects Redox Homeostasis in the Endoplasmic Reticulum

ABSTRACT: Lipoprotein Lipase (LPL) is a secreted lipase that clears triglycerides from the blood. Proper LPL folding and exit from the endoplasmic reticulum (ER) requires Lipase Maturation Factor 1 (LMF1), an ER resident trans-membrane protein, but the mechanism involved is unknown. We used proteomics to identify LMF1 binding partners necessary for LPL secretion in HEK293 cells and found these to include oxidoreductases and lectin chaperones, suggesting that LMF1 facilitates the formation of LPL's five disulfide bonds. In accordance with this role we found that LPL aggregates in LMF1-deficient cells due to the formation of incorrect intermolecular disulfide bonds. Cells lacking LMF1 were hypersensitive to depletion of glutathione, but not DTT treatment, suggesting that LMF1 helps reduce the ER. Accordingly, we found that loss of LMF1 results in a more oxidized ER. Our data show that LMF1 has a broader role than simply folding lipases and we identified fibronectin and the low-density lipoprotein receptor (LDLR) as novel LMF1 clients that contain multiple, non-sequential disulfide bonds. We conclude that LMF1 is needed for secretion of some ER client proteins that require reduction of non-native disulfides during their folding.

SUBMITTER: Benjamin, S Roberts

PROVIDER: S-SCDT-EMBOJ-2017-97379 | biostudies-other |

REPOSITORIES: biostudies-other

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Correction: Prion Protein Misfolding Affects Calcium Homeostasis and Sensitizes Cells to Endoplasmic Reticulum Stress.

Project description:[This corrects the article DOI: 10.1371/journal.pone.0015658.].

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