Brunetti Dario, Dykstra Werner, Le Stephanie, Zink Annika, Prigione Alessandro
Mitochondrial Medicine Laboratory, Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
Stem Cells. 2021 Oct;39(10):1289-1297. doi: 10.1002/stem.3425. Epub 2021 Jun 5.
Mitochondria are organelles with recognized key roles in cellular homeostasis, including bioenergetics, redox, calcium signaling, and cell death. Mitochondria are essential for neuronal function, given the high energy demands of the human brain. Consequently, mitochondrial diseases affecting oxidative phosphorylation (OXPHOS) commonly exhibit neurological impairment. Emerging evidence suggests that mitochondria are important not only for mature postmitotic neurons but also for the regulation of neural progenitor cells (NPCs) during the process of neurogenesis. These recent findings put mitochondria as central regulator of cell fate decisions during brain development. OXPHOS mutations may disrupt the function of NPCs and thereby impair the metabolic programming required for neural fate commitment. Promoting the mitochondrial function of NPCs could therefore represent a novel interventional approach against incurable mitochondrial diseases.
线粒体是在细胞内稳态中发挥公认关键作用的细胞器，包括生物能量学、氧化还原、钙信号传导和细胞死亡等方面。鉴于人类大脑对能量的高需求，线粒体对于神经元功能至关重要。因此，影响氧化磷酸化（OXPHOS）的线粒体疾病通常会表现出神经功能障碍。新出现的证据表明，线粒体不仅对成熟的有丝分裂后神经元很重要，而且在神经发生过程中对神经祖细胞（NPCs）的调节也很重要。这些最新发现使线粒体成为大脑发育过程中细胞命运决定的核心调节因子。OXPHOS突变可能会破坏NPCs的功能，从而损害神经命运决定所需的代谢编程。因此，促进NPCs的线粒体功能可能代表一种针对无法治愈的线粒体疾病的新型干预方法。
