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One hundred and fifty years ago, Johann Thudichum described sphingolipids as unusual "Sphinx-like" lipids from the brain. Today, we know that thousands of sphingolipid molecules mediate many essential functions in embryonic development and normal physiology. In addition, sphingolipid metabolism and signalling pathways are dysregulated in a wide range of pathologies, and therapeutic agents that target sphingolipids are now used to treat several human diseases. However, our understanding of sphingolipid regulation at cellular and organismal levels and their functions in developmental, physiological and pathological settings is rudimentary. In this Review, we discuss recent advances in sphingolipid pathways in different organelles, how secreted sphingolipid mediators modulate physiology and disease, progress in sphingolipid-targeted therapeutic and diagnostic research, and the trans-cellular sphingolipid metabolic networks between microbiota and mammals. Advances in sphingolipid biology have led to a deeper understanding of mammalian physiology and may lead to progress in the management of many diseases.
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http://dx.doi.org/10.1038/s41580-024-00742-y | DOI Listing |
Curr Opin Lipidol
August 2025
Cardiometabolic Immunity Laboratory, Department of Physiology, Monash Biomedicine Discovery Institute (BDI) and Victorian Heart Institute (VHI), Monash University, Melbourne, Victoria, Australia.
Purpose Of Review: This review explores the evolving understanding of efferocytosis - the clearance of dead or dying cells by phagocytes - in the context of atherosclerosis. It highlights recent discovers in cell death modalities, impaired clearance mechanisms and emerging therapeutic strategies aimed at restoring efferocytosis to stabilize plaques and resolve inflammation.
Recent Findings: Recent studies have expanded the scope of efferocytosis beyond apoptotic cells to include other pro-inflammatory cell death modes, including pyroptosis, necroptosis and ferroptosis, revealing context-dependent clearance efficiency and immunological outcomes.
Cell Physiol Biochem
September 2025
Department of Histology and Embryology and Vascular Biology Student Research Club, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland, E-Mail:
Migrasomes are newly discovered, migration-dependent organelles that mediate the release of cellular contents into the extracellular environment through a process known as migracytosis. Since their identification in 2014, growing evidence has highlighted their critical roles in intercellular communication, organ development, mitochondrial quality control, and disease pathogenesis. Migrasome biogenesis is a complex, multi-step process tightly regulated by lipid composition, tetraspanin-enriched microdomains, and molecular pathways involving sphingomyelin synthase 2, Rab35, and integrins.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Rehabilitation Medicine, Second Xiangya Hospital, Central South University, Changsha 410011.
Objectives: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Pathology, First Clinical College, Changzhi Medical College, Changzhi 046000.
Objectives: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases.
View Article and Find Full Text PDFZhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Urology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Objectives: Bladder cancer is a common malignancy with high incidence and poor prognosis. N-methyladenosine (mA) modification is widely involved in diverse physiological processes, among which the mA recognition protein YTH N-methyladenosine RNA binding protein F2 (YTHDF2) plays a crucial role in bladder cancer progression. This study aims to elucidate the molecular mechanism by which O-linked -acetylglucosamine (O-GlcNAc) modification of YTHDF2 regulates its downstream target, period circadian regulator 1 (), thereby promoting bladder cancer cell proliferation.
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