Gaynor P M, Hubbell S, Schmidt A J, Lina R A, Minskoff S A, Greenberg M L
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor 48109-0606.
J Bacteriol. 1991 Oct;173(19):6124-31. doi: 10.1128/jb.173.19.6124-6131.1991.
Phosphatidylglycerolphosphate synthase (PGPS; CDP-diacylglycerol glycerol 3-phosphate 3-phosphatidyltransferase; EC 2.7.8.5) catalyzes the first step in the synthesis of cardiolipin, an acidic phospholipid found in the mitochondrial inner membrane. In the yeast Saccharomyces cerevisiae, PGPS expression is coordinately regulated with general phospholipid synthesis and is repressed when cells are grown in the presence of the phospholipid precursor inositol (M. L. Greenberg, S. Hubbell, and C. Lam, Mol. Cell. Biol. 8:4773-4779, 1988). In this study, we examined the regulation of PGPS in growth conditions affecting mitochondrial development (carbon source, growth stage, and oxygen availability) and in strains with genetic lesions affecting mitochondrial function. PGPS derepressed two- to threefold when cells were grown in a nonfermentable carbon source (glycerol-ethanol), and this derepression was independent of the presence of inositol. PGPS derepressed two- to fourfold as cells entered the stationary phase of growth. Stationary-phase derepression occurred in both glucose- and glycerol-ethanol-grown cells and was slightly greater in cells grown in the presence of inositol and choline. PGPS expression in mitochondria was not affected when cells were grown in the absence of oxygen. In mutants lacking mitochondrial DNA [( rho0] mutants), PGPS activity was 30 to 70% less than in isogenic [rho+] strains. PGPS activity in [rho0] strains was subject to inositol-mediated repression. PGPS activity in [rho0] cell extracts was derepressed twofold as the [rho0] cells entered the stationary phase of growth. No growth phase derepression was observed in mitochondrial extracts of the [rho0] cells. Relative cardiolipin content increased in glycerol-ethanol-grown cells but was not affected by growth stage or by growth in the presence of the phospholipid precursors inositol and choline. These results demonstrate that (i) PGPS expression is regulated by factors affecting mitochondrial development; (ii) regulation of PGPS by these factors is independent of cross-pathway control; and (iii) PGPS expression is never fully repressed, even during anaerobic growth.
磷脂酰甘油磷酸合酶（PGPS；CDP - 二酰甘油甘油3 - 磷酸3 - 磷脂酰转移酶；EC 2.7.8.5）催化心磷脂合成的第一步，心磷脂是一种存在于线粒体内膜的酸性磷脂。在酿酒酵母中，PGPS的表达与一般磷脂合成协同调节，当细胞在磷脂前体肌醇存在的情况下生长时会受到抑制（M. L. 格林伯格、S. 哈贝尔和C. 林，《分子细胞生物学》8:4773 - 4779，1988）。在本研究中，我们研究了在影响线粒体发育的生长条件（碳源、生长阶段和氧气可用性）下以及在具有影响线粒体功能的基因损伤的菌株中PGPS的调控情况。当细胞在不可发酵碳源（甘油 - 乙醇）中生长时，PGPS的表达解除抑制两到三倍，并且这种解除抑制与肌醇的存在无关。当细胞进入生长稳定期时，PGPS的表达解除抑制两到四倍。稳定期解除抑制在葡萄糖和甘油 - 乙醇培养的细胞中均会发生，并且在肌醇和胆碱存在的情况下生长的细胞中解除抑制程度略高。当细胞在无氧条件下生长时，线粒体中PGPS的表达不受影响。在缺乏线粒体DNA的突变体（[rho0]突变体）中，PGPS活性比同基因的[rho +]菌株低30%至70%。[rho0]菌株中的PGPS活性受到肌醇介导的抑制。当[rho0]细胞进入生长稳定期时，[rho0]细胞提取物中的PGPS活性解除抑制两倍。在[rho0]细胞的线粒体提取物中未观察到生长阶段的解除抑制。甘油 - 乙醇培养的细胞中心磷脂的相对含量增加，但不受生长阶段或磷脂前体肌醇和胆碱存在情况下生长的影响。这些结果表明：（i）PGPS的表达受影响线粒体发育的因素调控；（ii）这些因素对PGPS的调控独立于交叉途径控制；（iii）即使在厌氧生长期间，PGPS的表达也从未被完全抑制。
