title: Sphingosine 1-phosphate (S1P) promotes mitochondrial biogenesis in Hep G2 cells by activating Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α).
abstract: Sphingosine 1-phosphate (S1P), a potent bioactive phospholipid, has been reported to regulate a broad spectrum of biological processes. However, little is known regarding S1P's effects on mitochondrial function. In this study, we investigated the S1P's effects on the Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway and mitochondrial biogenesis in Hep G2 cells. Our results indicate that administration of S1P leads to a significant upregulation of mitochondrial DNA replication and transcription, increased mitochondrial mass, and elevated adenosine triphosphate synthesis. In addition, we found that treatment with S1P stimulates expression of PGC-1α, a master regulator of mitochondrial biogenesis, as well as its downstream targets: nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Moreover, our data demonstrate that S1P's effects on PGC-1α and mitochondrial biogenesis are mediated by the protein kinase A/cAMP response element-binding protein (PKA/CREB) pathway. Importantly, we also revealed that S1P's effects on mitochondrial biogenesis are dependent on its type 2 receptor (S1P2), though not on either its type 1 (S1P1) or type 3 (S1P3) receptors. Based on these observations, we concluded that S1P activates the PKA/CREB pathway through S1P2, which then promotes expression of PGC-1α/NRF1/TFAM and subsequent mitochondrial biogenesis in Hep G2 cells.
authors.affiliation: Clinical Hospital of Weifang Medical University, Weifang, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Shen
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.forename: Pingping
authors.initials: P
authors.lastname: Liu
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhao
authors.forename: Wanpeng
authors.initials: W
authors.lastname: Xu
mesh_terms: D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics; D056945:Hep G2 Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004272:DNA, Mitochondrial; D008246:Lysophospholipids; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; C060506:sphingosine 1-phosphate; D013110:Sphingosine