Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles

Authors:

Ilham Kadhim1, Nazneen Begum1, William King1, Licheng Xu1 and Fusheng Tang1
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Affiliations:

1 Department of Biology, University of Arkansas, Little Rock, AR 72204, USA.

Keywords: 

Osh6, PI4P, Golgi, vacuole, longevity

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Corresponding Author(s):

Fusheng Tang, Department of Biology, FH 406, University of Arkansas at Little Rock, 2801 S. University Ave., Little Rock, AR 72204-1099; Tel: 501-569-3270; Fax: 501-569-3271; fxtang@ualr.edu

Conflict of interest statement:

The authors declare that they have no conflict of interest.

Please cite this article as:

Ilham Kadhim, Nazneen Begum, William King, Licheng Xu and Fusheng Tang (2022). Up-regulation of Osh6 boosts an anti-aging membrane trafficking pathway toward vacuoles. Microbial Cell 9(8): 145-157. doi: 10.15698/mic2022.08.783

© 2022 Kadhim et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

Members of the family of oxysterol-binding proteins mediate non-vesicular lipid transport between membranes and contribute to longevity in different manners. We previously found that a 2-fold up-regulation of Osh6, one of seven yeast oxysterol-binding proteins, remedies vacuolar morphology defects in mid-aged cells, partly down-regulates the target of rapamycin complex 1 (TORC1), and increases the replicative lifespan. At the molecular level, Osh6 transports phosphatidylserine (PS) and phosphatidylinositol-4-phosphate (PI4P) between the endoplasmic reticulum (ER) and the plasma membrane (PM). To decipher how an ER-PM working protein controls vacuolar morphology, we tested genetic interactions between OSH6 and DRS2, whose protein flips PS from the lumen to the cytosolic side of the Golgi, the organelle between ER and vacuoles in many pathways. Up-regulated OSH6 complemented vacuolar morphology of drs2∆ and enriched PI4P on the Golgi, indicating that Osh6 also works on the Golgi. This altered PI4P-enrichment led to a delay in the secretion of the proton ATPase Pma1 to the PM and a rerouting of Pma1 to vacuoles in a manner dependent on the trans-Golgi network (TGN) to late endosome (LE) trafficking pathway. Since the TGN-LE pathway controls endosomal and vacuolar TORC1, it may be the anti-aging pathway boosted by up-regulated Osh6.

doi: 10.15698/mic2022.08.783
Volume 9, pp. 145 to 157, published 15/07/2022.