Altered Sphingolipids Metabolism Damaged Mitochondrial Functions: Lessons Learned From Gaucher and Fabry Diseases

Journal of Clinical Medicine

Margarita Ivanova¹ 

[1] Lysosomal and Rare Disorders Research and Treatment Center, Faitfax, VA 22030, USA;

关键词: Gaucher disease;    Fabry disease;    sphingolipids;    mitochondria;    autophagy;   

DOI  :  10.3390/jcm9041116

来源: DOAJ

【 摘 要 】

Sphingolipids represent a class of bioactive lipids that modulate the biophysical properties of biological membranes and play a critical role in cell signal transduction. Multiple studies have demonstrated that sphingolipids control crucial cellular functions such as the cell cycle, senescence, autophagy, apoptosis, cell migration, and inflammation. Sphingolipid metabolism is highly compartmentalized within the subcellular locations. However, the majority of steps of sphingolipids metabolism occur in lysosomes. Altered sphingolipid metabolism with an accumulation of undigested substrates in lysosomes due to lysosomal enzyme deficiency is linked to lysosomal storage disorders (LSD). Trapping of sphingolipids and their metabolites in the lysosomes inhibits lipid recycling, which has a direct effect on the lipid composition of cellular membranes, including the inner mitochondrial membrane. Additionally, lysosomes are not only the house of digestive enzymes, but are also responsible for trafficking organelles, sensing nutrients, and repairing mitochondria. However, lysosomal abnormalities lead to alteration of autophagy and disturb the energy balance and mitochondrial function. In this review, an overview of mitochondrial function in cells with altered sphingolipid metabolism will be discussed focusing on the two most common sphingolipid disorders, Gaucher and Fabry diseases. The review highlights the status of mitochondrial energy metabolism and the regulation of mitochondria–autophagy–lysosome crosstalk.

【 授权许可】

Unknown