GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth

Nagaraj, Meghana, Höring, Marcus, Ahonen, Maria A., Nguyen, Van Dien, Zhou, You ORCID: https://orcid.org/0000-0002-1743-1291, Vihinen, Helena, Jokitalo, Eija, Liebisch, Gerhard, Nidhina Haridas, P.A. and Olkkonen, Vesa M. 2022. GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth. Journal of Lipid Research 63 (9) , 100259. 10.1016/j.jlr.2022.100259

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Abstract

Golgi membrane protein 1 (GOLM1) is a Golgi-resident type 2 transmembrane protein known to be overexpressed in several cancers, including hepatocellular carcinoma (HCC), as well as in viral infections. However, the role of GOLM1 in lipid metabolism remains enigmatic. In this study, we employed siRNA-mediated GOLM1 depletion in Huh-7 HCC cells to study the role of GOLM1 in lipid metabolism. Mass spectrometric lipidomic analysis in GOLM1 knockdown cells showed an aberrant accumulation of sphingolipids, such as ceramides, hexosylceramides, dihexosylceramides, sphinganine, sphingosine, and ceramide phosphate, along with cholesteryl esters. Furthermore, we observed a reduction in phosphatidylethanolamines and lysophosphatidylethanolamines. In addition, Seahorse extracellular flux analysis indicated a reduction in mitochondrial oxygen consumption rate upon GOLM1 depletion. Finally, alterations in Golgi structure and distribution were observed both by electron microscopy imaging and immunofluorescence microscopy analysis. Importantly, we found that GOLM1 depletion also affected cell proliferation and cell cycle progression in Huh-7 HCC cells. The Golgi structural defects induced by GOLM1 reduction might potentially affect the trafficking of proteins and lipids leading to distorted intracellular lipid homeostasis, which may result in organelle dysfunction and altered cell growth. In conclusion, we demonstrate that GOLM1 depletion affects sphingolipid metabolism, mitochondrial function, Golgi structure, and proliferation of HCC cells.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2022-07-24
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0022-2275
Date of First Compliant Deposit:	12 September 2022
Last Modified:	21 May 2023 16:48
URI:	https://orca.cardiff.ac.uk/id/eprint/152498

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