PMID- 36902011
OWN - NLM
STAT- MEDLINE
DCOM- 20230314
LR  - 20230314
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 5
DP  - 2023 Feb 26
TI  - S1P Released by SGPL1-Deficient Astrocytes Enhances Astrocytic ATP Production via 
      S1PR(2,4), Thus Keeping Autophagy in Check: Potential Consequences for Brain 
      Health.
LID - 10.3390/ijms24054581 [doi]
LID - 4581
AB  - Astrocytes are critical players in brain health and disease. 
      Sphingosine-1-phosphate (S1P), a bioactive signaling lipid, is involved in 
      several vital processes, including cellular proliferation, survival, and 
      migration. It was shown to be crucial for brain development. Its absence is 
      embryonically lethal, affecting, inter alia, the anterior neural tube closure. 
      However, an excess of S1P due to mutations in S1P-lyase (SGPL1), the enzyme 
      responsible for its constitutive removal, is also harmful. Of note, the gene 
      SGPL1 maps to a region prone to mutations in several human cancers and also in 
      S1P-lyase insufficiency syndrome (SPLIS) characterized by several symptoms, 
      including peripheral and central neurological defects. Here, we investigated the 
      impact of S1P on astrocytes in a mouse model with the neural-targeted ablation of 
      SGPL1. We found that SGPL1 deficiency, and hence the accumulation of its 
      substrate, S1P, causes the elevated expression of glycolytic enzymes and 
      preferentially directs pyruvate into the tricarboxylic acid (TCA) cycle through 
      its receptors (S1PR(2,4)). In addition, the activity of TCA regulatory enzymes 
      was increased, and consequently, so was the cellular ATP content. The high energy 
      load activates the mammalian target of rapamycin (mTOR), thus keeping astrocytic 
      autophagy in check. Possible consequences for the viability of neurons are 
      discussed.
FAU - Alam, Shah
AU  - Alam S
AUID- ORCID: 0000-0002-5806-5603
AD  - LIMES Institute for Membrane Biology and Lipid Biochemistry, Kekule-Institute, 
      University of Bonn, 53115 Bonn, Germany.
FAU - Afsar, Sumaiya Yasmeen
AU  - Afsar SY
AD  - LIMES Institute for Membrane Biology and Lipid Biochemistry, Kekule-Institute, 
      University of Bonn, 53115 Bonn, Germany.
FAU - Van Echten-Deckert, Gerhild
AU  - Van Echten-Deckert G
AUID- ORCID: 0000-0002-2816-7852
AD  - LIMES Institute for Membrane Biology and Lipid Biochemistry, Kekule-Institute, 
      University of Bonn, 53115 Bonn, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230226
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - NGZ37HRE42 (Sphingosine)
RN  - 0 (Lysophospholipids)
RN  - EC 4.1.2.- (Aldehyde-Lyases)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 4.1.2.27 (SGPL1 protein, human)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - *Astrocytes/metabolism
MH  - *Sphingosine/metabolism
MH  - Brain/metabolism
MH  - Lysophospholipids/metabolism
MH  - Aldehyde-Lyases/genetics
MH  - Autophagy/physiology
MH  - Adenosine Triphosphate/metabolism
MH  - Mammals/metabolism
PMC - PMC10003137
OTO - NOTNLM
OT  - S1P-lyase (SGPL1)
OT  - SPLIS
OT  - autophagy
OT  - glucose metabolism
OT  - sphingosine 1-phosphate (S1P)
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/12 06:00
MHDA- 2023/03/15 06:00
PMCR- 2023/02/26
CRDT- 2023/03/11 01:16
PHST- 2023/02/06 00:00 [received]
PHST- 2023/02/22 00:00 [revised]
PHST- 2023/02/24 00:00 [accepted]
PHST- 2023/03/11 01:16 [entrez]
PHST- 2023/03/12 06:00 [pubmed]
PHST- 2023/03/15 06:00 [medline]
PHST- 2023/02/26 00:00 [pmc-release]
AID - ijms24054581 [pii]
AID - ijms-24-04581 [pii]
AID - 10.3390/ijms24054581 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Feb 26;24(5):4581. doi: 10.3390/ijms24054581.