The Bis(monoacylglycero)-phosphate Hypothesis: From Lysosomal Function to Therapeutic Avenues.
Annu Rev Biochem
; 93(1): 447-469, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38603559
ABSTRACT
Lysosomes catabolize and recycle lipids and other biological molecules to maintain cellular homeostasis in diverse nutrient environments. Lysosomal lipid catabolism relies on the stimulatory activity of bis(monoacylglycero)phosphate (BMP), an enigmatic lipid whose levels are altered across myriad lysosome-associated diseases. Here, we review the discovery of BMP over half a century ago and its structural properties that facilitate the activation of lipid hydrolases and recruitment of their coactivators. We further discuss the current, yet incomplete, understanding of BMP catabolism and anabolism. To conclude, we discuss its role in lysosome-associated diseases and the potential for modulating its levels by pharmacologically activating and inhibiting the BMP synthase to therapeutically target lysosomal storage disorders, drug-induced phospholipidosis, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, cancer, and viral infection.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Lisofosfolipídeos
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Doenças por Armazenamento dos Lisossomos
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Monoglicerídeos
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Lisossomos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Annu Rev Biochem
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos