PLS3 (phospholipid scramblase-3) is a new member of the family of phospholipid scramblases and transports CL (cardiolipin) from the inner to the outer mitochondrial membrane. In the present paper we examined whether changing the levels of functional PLS3 in HeLa cells altered de novo CL biosynthesis and its resynthesis. HeLa cells overexpressing PLS3 or expressing a disrupted PLS3 (F258V) or control were incubated with [1,3-3H]glycerol and radioactivity incorporated into CL was determined. CL biosynthesis from [1,3-3H]glycerol was increased 1.8-fold in PLS3 cells and 2.1-fold in F258V cells compared with control. This was due to a 64% (P<0.05) and 2.6-fold (P<0.05) elevation in CL synthase activity in PLS3 and F258V cells respectively, compared with control, and not due to changes in phosphatidylglycerolphosphate synthase activity. The increase in CL synthase activity in these cells was due to an increase in its mRNA expression. In contrast, resynthesis of CL from [1-14C]linoleic acid was reduced 52% (P<0.05) in PLS3 and 45% (P<0.05) in F258V cells compared with control and this was due to a reduction in mitochondrial monolysocardiolipin acyltransferase activity. Although protein levels of mitochondrial monolysocardiolipin acyltransferase were unaltered, activity and mRNA expression of endoplasmic reticulum monolysocardiolipin acyltransferase was upregulated in PLS3 and F258V cells compared with controls. These data indicate that the CL resynthesis in HeLa cells is sensitive to the mitochondrial localization of CL and not the level of the reacylating enzymes. Alterations in functional PLS3 levels in PLS3 or F258V cells did not affect the mitochondrial decarboxylation of phosphatidylserine to phosphatidylethanolamine indicating that the biosynthetic changes to CL were specific for this mitochondrial phospholipid. We hypothesize that the cardiolipin resynthesis machinery in the cell ‘senses’ altered levels of CL on mitochondrial membranes and that de novo CL biosynthesis is up-regulated in HeLa cells as a compensatory mechanism in response to altered movement of mitochondrial CL. The results identify PLS3 as a novel regulator of CL de novo biosynthesis and its resynthesis.
Skip Nav Destination
Article navigation
January 2007
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
December 11 2006
Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells
Quyen Van;
Quyen Van
*Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T6
Search for other works by this author on:
Jihua Liu;
Jihua Liu
†University of Utah, Salt Lake City, Utah 84112, U.S.A.
Search for other works by this author on:
Biao Lu;
Biao Lu
‡Department of Medicine, University of California, San Francisco, CA 94121, U.S.A.
Search for other works by this author on:
Kenneth R. Feingold;
Kenneth R. Feingold
‡Department of Medicine, University of California, San Francisco, CA 94121, U.S.A.
Search for other works by this author on:
Yuguang Shi;
Yuguang Shi
§Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, U.S.A.
Search for other works by this author on:
Ray M. Lee;
Ray M. Lee
∥Virginia Commonwealth University, Richmond, VA 23298, U.S.A.
Search for other works by this author on:
Grant M. Hatch
Grant M. Hatch
1
*Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T6
¶Departments of Biochemistry and Medical Genetics, Internal Medicine and Center for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Manitoba, Canada, R3E 0T6
1To whom correspondence should be addressed (email hatchgm@ms.umanitoba.ca).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 08 2006
Revision Received:
August 10 2006
Accepted:
August 29 2006
Accepted Manuscript online:
August 29 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2007
Biochem J (2007) 401 (1): 103–109.
Article history
Received:
March 08 2006
Revision Received:
August 10 2006
Accepted:
August 29 2006
Accepted Manuscript online:
August 29 2006
Citation
Quyen Van, Jihua Liu, Biao Lu, Kenneth R. Feingold, Yuguang Shi, Ray M. Lee, Grant M. Hatch; Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells. Biochem J 1 January 2007; 401 (1): 103–109. doi: https://doi.org/10.1042/BJ20060373
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.