Luévano-Martínez Luis Alberto, Forni Maria Fernanda, dos Santos Valquiria Tiago, Souza-Pinto Nadja C, Kowaltowski Alicia J
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Cidade Universitária, Av. Prof. Lineu Prestes, 748, São Paulo, SP 05508-000, Brazil.
Biochim Biophys Acta. 2015 Jun-Jul;1847(6-7):587-98. doi: 10.1016/j.bbabio.2015.03.007. Epub 2015 Apr 2.
Mitochondria play a key role in adaptation during stressing situations. Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins. Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. Interestingly, we found that thermal stress promotes a 30% increase in the cardiolipin content and modifies the physical state of mitochondrial membranes. These changes have effects on mtDNA stability, adapting cells to thermal stress. Conversely, this effect is cardiolipin-dependent since a cardiolipin synthase-null mutant strain is unable to adapt to thermal stress as observed by a 60% increase of cells lacking mtDNA (ρ0). Interestingly, we found that the loss of cardiolipin specifically affects the segregation of mtDNA to daughter cells, leading to a respiratory deficient phenotype after replication. We also provide evidence that mtDNA physically interacts with cardiolipin both in S. cerevisiae and in mammalian mitochondria. Overall, our results demonstrate that the mitochondrial lipid cardiolipin is a key determinant in the maintenance of mtDNA stability and segregation.
线粒体在应激情况下的适应性过程中发挥关键作用。心磷脂作为线粒体膜中的主要阴离子磷脂，有望成为这种适应性机制的一个决定因素，因为它能调节大多数膜蛋白的活性。在此，我们以酿酒酵母为模型，使其处于影响线粒体代谢的条件下，以确定心磷脂在应激适应中的可能作用。有趣的是，我们发现热应激会使心磷脂含量增加30%，并改变线粒体膜的物理状态。这些变化对线粒体DNA（mtDNA）的稳定性产生影响，使细胞适应热应激。相反，这种效应依赖于心磷脂，因为正如缺乏mtDNA（ρ0）的细胞增加60%所观察到的那样，心磷脂合酶缺失突变株无法适应热应激。有趣的是，我们发现心磷脂的缺失特别影响mtDNA向子细胞的分离，导致复制后出现呼吸缺陷表型。我们还提供证据表明，在酿酒酵母和哺乳动物线粒体中，mtDNA均与心磷脂发生物理相互作用。总体而言，我们的结果表明，线粒体脂质心磷脂是维持mtDNA稳定性和分离的关键决定因素。
