Cell Cycle Regulation of Membrane Phospholipid Metabolism

Abstract

This review focuses on the phospholipid metabolism regulated by the cell cycle. Phospholipids are the major cellular constituents required for the assembly of biological membranes, and cells must double their phospholipid mass to form daughter cells. It seems reasonable that this event should coincide with the synthesis of other cellular components such as DNA, stable RNA, etc.; however, the biochemical mechanisms that coordinate macromolecular and bulk membrane phospholipid production are largely unknown. The importance of these regulatory processes to cell physiology is obvious. Discordant regulation of phospholipid accumulation by only a few percent per cell cycle would rapidly result in cells with either a large excess or deficit of membrane surface leading to abnormalities in cell size and/or intracellular lipid accumulation. Thus, stringent control mechanisms must be in place to keep the phospholipid content in tune with the cell cycle. This discussion will explore the state of our knowledge in cultured mammalian cell systems, although cell cycle-regulated phospholipid accumulation occurs in lower eukaryotes such as Saccharomyces cerevisiae (1) and Caulobacter crescentus (2). This review is limited to a discussion of events that are directly tied to the cell cycle. Phospholipid metabolism in response to mitogenic stimulation will not be addressed as these biochemical events are generally associated with the G 0 to G 1 transition and are ligand-regulated rather than being orchestrated by the cell cycle. G 1 PhaseThe G 1 phase of the cell cycle is characterized as having a high rate of membrane phospholipid turnover. Increased incorporation of label into phospholipids and elevated levels of intracellular soluble phospholipid precursors were noted after the mitogenic stimulation of cells (3, 4), although these studies did not address whether the increase in labeling represented net phospholipid synthesis or enhanced phospholipid turnover (5-11). Jackowski (12) examined both synthesis and degradation in a macrophage cell line using a double label experiment and attributed the increase in choline incorporation into PtdCho 1 during G 1 (4) to rapid PtdCho turnover (12). Importantly, the rate of PtdCho degradation decreased by an order of magnitude in S phase and then accelerated again as the cells entered the next G 1 period, thereby establishing that PtdCho turnover in G 1 was associated with the cell cycle and not a property of the G 0 to G 1 transition (12). The cessation of PtdCho degradation in S phase is likely an important contributor to the net accumulation of phospholipid during this time; however, nothing is known about the biochemical processes that govern the periodicity of PtdCho turnover. PtdCho turnover may be an important aspect of phospholipid metabolism during G 1 that is necessary, and in some cases, sufficient for entry into S phase. PtdCho hydrolysis by phospholipase C and/or D pathways is triggered by a wide array of agonists (9), and both exogenous bacterial PtdCho phospholipase C (13) and...

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Transcript level coordination of carbon pathways during silicon starvation‐induced lipid accumulation in the diatom Thalassiosira pseudonana

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