Hepatic lysosomal lipid remodeling in cold adaptation: Insights into TFEB-PLA2G15-BMP axis regulation

Acknowledgement

Not applicable.

Author contributions

Omar JM: Writing, review and editing, writing original draft. Liu Y H: Writing, review and editing, writing original draft, supervision.

Informed consent

Not applicable.

Ethical approval

Not applicable.

Use of large language models, AI and machine learning tools

No Generative Al was used in the preparation of this manuscript.

Conflict of interest

The authors declare that there are no conflicts of interest.

Data availability statement

Not applicable.

References

[1] Davidson J W, Jain R, T Kizzar T, et al. Hepatic lipid remodeling in cold exposure uncovers direct regulation of bis(monoacylglycero) phosphate lipids by phospholipase A 2 group XV. Cell Metab, 2025; 37(6): 1413-1425 e6.

[2] Showalter M R, Berg A L, Nagourney A, et al. The emerging and diverse roles of bis(monoacylglycero) phosphate lipids in cellular physiology and disease. Int J Mol Sci, 2020; 21(21): 8067.

[3] Grabner G F, Fawzy N, Schreiber R, et al. Metabolic regulation of the lysosomal cofactor bis(monoacylglycero)phosphate in mice. J Lipid Res, 2020; 61(7): 995-1003.

[4] Settembre C, de Cegli R, G Mansueto, et al. TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol, 2013; 15(6): 647-658.

[5] Nyame K, Xiong J, Alsohybe H N, et al. PLA2G 15 is a lysosomal BMP hydrolase and its targeting ameliorates lysosomal disease. Nature, 2025; 642(8067): 474-483.

[6] Boland S, Swarup S, Ambaw Y A, et al. Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis. Nat Commun, 2022; 13(1): 5924.

[7] Kirkegaard T, Roth A G, Petersen N H, et al. Hsp 70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature, 2010; 463(7280): 549-553.

[8] Zhang S, Williams K J, Verlande-Ferrero A, et al. Acute activation of adipocyte lipolysis reveals dynamic lipid remodeling of the hepatic lipidome. J Lipid Res, 2024; 65(2): 100434.

[9] Karpe F, Pinnick K E. Biology of upper-body and lower-body adipose tissue--link to whole-body phenotypes. Nat Rev Endocrinol, 2015; 11(2): 90-100.

[10] Herzig S, Shaw R J. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol, 2018; 19(2): 121-135.

[11] Medina D L, Di Paola S, Peluso I, et al. Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol, 2015; 17(3): 288-299.

[12] Decressac M, Mattsson B, Weikop P, et al. TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc Natl Acad Sci U S A, 2013; 110(19): E1817-1826.

[13] Alvarez-Valadez K, Sauvat A, Diharce J, et al. Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death. Autophagy, 2025; 21(5): 934-956.

[14] Anderson D MG, Ablonczy Z, Koutalos Y, et al. Bis(monoacylglycero) phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas. Sci Rep, 2017; 7(1): 17352.

[15] Glukhova A, Hinkovska-Galcheva V, Kelly R, et al. Structure and function of lysosomal phospholipase A2 and lecithin: cholesterol acyltransferase. Nat Commun, 2015; 6: 6250. Relative Articles