On April 8, 2025, the research group led by Professor Zhou Hong from the School of Life Sciences at our university published a research article entitled Sphingosine kinase 2 deficiency impairs VLDL secretion by inhibiting mTORC2 phosphorylation and activating chaperone-mediated autophagy in the authoritative journal on cell fate regulation, Cell Death & Differentiation (a top-ranked journal in the Chinese Academy of Sciences Category I, IF=13.7).The work was co-authored by Zhang Shuangshuang (a Master student of batch 2020) and Li Gaoxiang(a Doctoral student of batch 2020), both serving as co-first authors of the paper. The first corresponding author and primary institution are both Anhui Medical University.
With the increasingly higher global prevalence of obesity and metabolic syndrome, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the most common chronic liver diseases worldwide, as well as a major cause of cirrhosis, liver cancer, and even liver transplantation. In this pivotal study, Professor Zhou’s team systematically elucidated that SphK2 (sphingosine kinase II) deficiency impairs the transport of VLDL (very low-density lipoprotein) vesicles to the Golgi apparatus by downregulating mTORC2 phosphorylation, which activates the CMA (chaperone-mediated autophagy) pathway and accelerates SNARE complex degradation, thus causing hepatic lipid accumulation. Importantly, the research identified a novel mTORC2-CMA-SNARE signaling axis, providing new insights into the regulatory mechanisms underlying hepatic lipid metabolic homeostasis.
In the context of rising MASLD incidence and increasing need for effective intervention strategiesother than exploratory ones, this research highlights SphK2 and its metabolic product sphingosine-1-phosphate (S1P) as potential therapeutic targets for MASLD. Additionally, it reveals novel functions of CMA in the regulation of metabolic diseases.
For further information, please see the full article: https://www.nature.com/articles/s41418-025-01507-6