Sphingosine kinase 1 overexpression induces MFN2 fragmentation and alters mitochondrial matrix Ca2+ handling in HeLa cells

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Pulli , I , Lof , C , Blom , T , Asghar , M Y , Lassila , T , Back , N , Lin , K-L , Nystrom , J H , Kemppainen , K , Toivola , D M , Dufour , E , Sanz , A , Cooper , H M , Parys , J B & Tornquist , K 2019 , ' Sphingosine kinase 1 overexpression induces MFN2 fragmentation and alters mitochondrial matrix Ca2+ handling in HeLa cells ' , Biochimica et Biophysica Acta. Molecular Cell Research , vol. 1866 , no. 9 , pp. 1475-1486 . https://doi.org/10.1016/j.bbamcr.2019.06.006

Title: Sphingosine kinase 1 overexpression induces MFN2 fragmentation and alters mitochondrial matrix Ca2+ handling in HeLa cells
Author: Pulli, Ilari; Lof, C.; Blom, T.; Asghar, M. Y.; Lassila, T.; Back, N.; Lin, K-L; Nystrom, J. H.; Kemppainen, K.; Toivola, D. M.; Dufour, E.; Sanz, A.; Cooper, H. M.; Parys, J. B.; Tornquist, K.
Contributor organization: Department of Anatomy
Medicum
Date: 2019-09
Language: eng
Number of pages: 12
Belongs to series: Biochimica et Biophysica Acta. Molecular Cell Research
ISSN: 0167-4889
DOI: https://doi.org/10.1016/j.bbamcr.2019.06.006
URI: http://hdl.handle.net/10138/318773
Abstract: Sphingosine kinase 1 (SKI) converts sphingosine to the bioactive lipid sphingosine 1-phosphate (SIP). SW binds to G-protein-coupled receptors (S1PR(1-5)) to regulate cellular events, including Ca2+ signaling. The SK1/S1P axis and Ca2+ signaling both play important roles in health and disease. In this respect, Ca2+ microdomains at the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are of importance in oncogenesis. Mitofusin 2 (MFN2) modulates ER-mitochondria contacts, and dysregulation of MFN2 is associated with malignancies. We show that overexpression of SKI augments agonist-induced Ca2+ release from the ER resulting in increased mitochondria] matrix Ca2+. Also, overexpression of SK1 induces MFN2 fragmentation, likely through increased calpain activity. Further, expressing putative calpain-cleaved MFN2 N- and C-terminal fragments increases mitochondrial matrix Ca2+ during agonist stimulation, mimicking the SK1 overexpression in cells. Moreover, SK1 overexpression enhances cellular respiration and cell migration. Thus, SK1 regulates MFN2 fragmentation resulting in increased mitochondrial Ca2+ and downstream cellular effects.
Subject: Mitochondria
Calcium
Sphingosine kinase
Sphingosine 1-phosphate
Mitofusin-2
Endoplasmic reticulum
ESSENTIAL COMPONENT
CALCIUM
PROTEIN
1-PHOSPHATE
MEMBRANE
DEFICIENCY
CONTACT
CALPAIN
DYSFUNCTION
METABOLISM
3111 Biomedicine
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion


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