Duarte Filipe V, Amorim Joao A, Palmeira Carlos M, Rolo Anabela P
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal. Department of Life Sciences, University of Coimbra, Coimbra 3000-456, Portugal.
Curr Med Chem. 2015;22(20):2468-79. doi: 10.2174/0929867322666150514095910.
Mitochondria are key players in the maintenance of cellular homeostasis, as they generate ATP via OXPHOS. As such, disruption in mitochondrial homeostasis is closely associated with disease states, caused by subtle alterations in the function of tissues or by major defects, particularly evident in tissues with high metabolic demands. Adaptations in mitochondrial copy number or mitochondrial mass, and the induction of genes implicated in OXPHOS or in intermediary metabolism as well, depend on the balanced contribution of both the nuclear and mitochondrial genomes. This forms a biogenesis program, controlled by several nuclear factors that act coordinately and in a categorized manner. Dynamic changes in mitochondrial regulators are associated with post-translational modifications mediated by metabolic sensors, such as SIRT1 and AMPK. Nrf2, which induces an antioxidant protective response against oxidative stress, also modulates bioenergetic function and metabolism. Additionally, the stability of mitochondrial transcripts is decreased by miRNA detected in the mitochondria, thus affecting the bioenergetic capacity of the cell. However, mitochondrial adaptation to metabolic demands is also dependent on the removal of damaged mitochondria (mitophagy) and fission/fusion events of the mitochondrial network.
线粒体是维持细胞内稳态的关键参与者，因为它们通过氧化磷酸化产生ATP。因此，线粒体稳态的破坏与疾病状态密切相关，这些疾病状态是由组织功能的细微改变或重大缺陷引起的，在代谢需求高的组织中尤为明显。线粒体拷贝数或线粒体质量的适应性变化，以及与氧化磷酸化或中间代谢相关基因的诱导，都依赖于核基因组和线粒体基因组的平衡贡献。这形成了一个生物发生程序，由几个以协调和分类方式起作用的核因子控制。线粒体调节因子的动态变化与由代谢传感器（如SIRT1和AMPK）介导的翻译后修饰有关。诱导针对氧化应激的抗氧化保护反应的Nrf2也调节生物能量功能和代谢。此外，线粒体中检测到的miRNA会降低线粒体转录本的稳定性，从而影响细胞的生物能量能力。然而，线粒体对代谢需求的适应性也依赖于受损线粒体的清除（线粒体自噬）以及线粒体网络的分裂/融合事件。
