Institute of Clinical Chemistry, Department of Pathobiochemistry, Medical Faculty, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.
Institute of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, University of Greifswald, Ferdinand-Sauerbruch-Str., D-17475 Greifswald, Germany.
Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Mar;1865(3):158596. doi: 10.1016/j.bbalip.2019.158596. Epub 2019 Dec 26.
The mitochondrial phospholipid (CL) has been linked to mitochondrial and cellular functions. It has been postulated that the composition of CL is of impact for mitochondrial energy metabolism and cell proliferation. Although a correlation between CL composition and proliferation could be demonstrated for several cell types, evidence for a causal relationship remains obscure. Here, we applied two independent approaches, i) supplementation of fatty acids and ii) knock-out of the phospholipid remodeling enzyme tafazzin, to manipulate CL composition and analyzed the response on proliferation of C6 glioma cells. Both strategies caused substantial changes in the distribution of cellular fatty acids as well as in the distribution of fatty acids incorporated in CL that were accompanied by changes of the composition of molecular CL species. These changes did not correlate with cell proliferation. However, knock-out of tafazzin caused dramatic reduction in proliferation of C6 glioma cells independent of CL composition. The mechanism of tafazzin-dependent restriction of proliferation remains unclear. Among the various fatty acids administered only palmitic acid restricted cell proliferation by induction of cell death.
线粒体磷脂（CL）与线粒体和细胞功能有关。有人假设，CL 的组成对线粒体能量代谢和细胞增殖有影响。尽管已经证明了 CL 组成与增殖之间存在相关性，但对于因果关系的证据仍然不清楚。在这里，我们应用了两种独立的方法，i）脂肪酸的补充和 ii）磷脂重塑酶 tafazzin 的敲除，来操纵 CL 的组成，并分析了对 C6 神经胶质瘤细胞增殖的反应。这两种策略都导致了细胞脂肪酸分布以及掺入 CL 的脂肪酸分布的实质性变化，同时伴随着 CL 分子种类组成的变化。这些变化与细胞增殖无关。然而，tafazzin 的敲除导致 C6 神经胶质瘤细胞的增殖明显减少，与 CL 的组成无关。tafazzin 依赖性增殖限制的机制尚不清楚。在所给予的各种脂肪酸中，只有棕榈酸通过诱导细胞死亡来限制细胞增殖。
