Lipidomics analysis of WT and CLN5-deficient HEK293T cells, iPSCs, and iNeurons
Data files
Nov 01, 2024 version files 5.83 GB
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101_N.raw
157.80 MB
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101_P.raw
122.68 MB
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102_N.raw
151.35 MB
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102_P.raw
123.46 MB
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103_N.raw
152.97 MB
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103_P.raw
124.68 MB
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11B_neg.raw
172.32 MB
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11B_pos.raw
126.49 MB
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12B_neg.raw
170.46 MB
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12B_pos.raw
125.82 MB
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13B_neg.raw
171.69 MB
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13B_pos.raw
125.62 MB
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14B_neg.raw
171.51 MB
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14B_pos.raw
127.32 MB
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51_N.raw
174.77 MB
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51_P.raw
122.28 MB
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52_N.raw
174.82 MB
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52_P.raw
121.58 MB
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53_N.raw
174.59 MB
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53_P.raw
121.16 MB
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91_N.raw
154.78 MB
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91_P.raw
123.31 MB
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91B_neg.raw
172.53 MB
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91B_pos.raw
126.48 MB
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92_N.raw
154.23 MB
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92_P.raw
121.73 MB
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92B_neg.raw
171.94 MB
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92B_pos.raw
125.47 MB
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93_N.raw
154.38 MB
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93_P.raw
121.70 MB
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93B_neg.raw
173.88 MB
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93B_pos_20230102182818.raw
125.91 MB
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94B_neg.raw
171.86 MB
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94B_pos.raw
124.95 MB
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README.md
563 B
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W1_N.raw
174.54 MB
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W1_P.raw
122.37 MB
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W2_N.raw
174.64 MB
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W2_P.raw
123.11 MB
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W3_N.raw
174.97 MB
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W3_P.raw
122.89 MB
Abstract
Lysosomes critically rely on bis(monoacylglycero)phosphate (BMP) to stimulate lipid catabolism, cholesterol homeostasis, and lysosomal function. Alterations in BMP levels in monogenic and complex neurodegeneration suggest an essential function in human health. However, the site and mechanism responsible for BMP synthesis have been subject to debate for decades. Here, we report that the Batten disease gene product CLN5 is the elusive BMP synthase (BMPS). BMPS-deficient cells exhibit a massive accumulation of the BMP synthesis precursor lysophosphatidylglycerol (LPG), depletion of BMP species, and dysfunctional lipid metabolism. Mechanistically, we demonstrate that BMPS mediates synthesis through an energy-independent base exchange reaction between two LPG molecules with increased activity on BMP-laden vesicles. Our study resolves the long-sought BMP biosynthetic route and reveals a novel anabolic function of late endosomes/lysosomes.
README
Lipidomics of CLN5-deficient and WT HEK293T cells, iPSCs, and iNeurons
Dataset contains raw files for analysis in free softwares FreeStyle and MS-DIAL.
Description of the Data and file structure
- P = positive mode
- N = negative mode
- Pos = positive mode
- Neg = negative mode
- B = LysoIP Fraction
- 101-103 = WT iPSCs
- 91-93 = CLN5 KO iPSCs
- 91B-94B = CLN5 KO HEK293Ts
- 11B-14B = WT HEK293Ts
- W1-3 = WT iNeurons
- 51-53 = CLN5 KO iNeurons
- "93B_pos_20230102182818" refers to 93B_pos
iPSCs, HEK293Ts, and iNeurons should be analyzed as groups