Nagaraj, Meghana and Höring, Marcus and Ahonen, Maria A. and Van Dien Nguyen, and Zhou, You and Vihinen, Helena and Jokitalo, Eija and Liebisch, Gerhard and 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. ISSN 0022-2275, 1539-7262
Full text not available from this repository. (Request a copy)Abstract
Golgi membrane protein 1 (GOLM1) is a Golgi-resident type 2 transmembrane protein known to be overexpressed in several cancers, including he-patocellular carcinoma (HCC), as well as in viral in-fections. 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 accu-mulation of sphingolipids, such as ceramides, hex-osylceramides, dihexosylceramides, sphinganine, sphingosine, and ceramide phosphate, along with cholesteryl esters. Furthermore, we observed a reduction in phosphatidylethanolamines and lyso-phosphatidylethanolamines. In addition, Seahorse extracellular flux analysis indicated a reduction in mitochondrial oxygen consumption rate upon GOLM1 depletion. Finally, alterations in Golgi struc-ture and distribution were observed both by electron microscopy imaging and immunofluorescence mi-croscopy 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 ho-meostasis, which may result in organelle dysfunction and altered cell growth. In conclusion, we demon-strate that GOLM1 depletion affects sphingolipid metabolism, mitochondrial function, Golgi structure, and proliferation of HCC cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEPATOCELLULAR-CARCINOMA CELLS; TANDEM MASS-SPECTROMETRY; LIPID EXTRACTION; GP73; EXPRESSION; PROTEIN; PROLIFERATION; EPIDEMIOLOGY; CERAMIDE; INVASION; ceramide; cholesteryl ester; glycosphingolipid; Golgi; GOLPH2; GP73; phosphatidylethanolamine; mitochondrial function; hexosylceramide; dihexosylceramide |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2024 13:47 |
| Last Modified: | 29 Jan 2024 14:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58254 |
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