Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Department of Biochemistry and Microbiology, Institute of Biology, Warsaw University of Life Sciences, 02-787 Warsaw, Poland.
Int J Mol Sci. 2023 Aug 22;24(17):13033. doi: 10.3390/ijms241713033.
Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they're not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions.
神经退行性疾病（NDs）是一组以神经元进行性退化和死亡为特征的多种疾病，导致一系列神经症状。尽管这些疾病存在异质性，但一个共同点是线粒体功能障碍在其发病机制中的作用。线粒体在生物分子的合成、通过氧化磷酸化（OXPHOS）产生的三磷酸腺苷（ATP）提供能量以及产生活性氧物种（ROS）方面发挥着关键作用。当它们不能正常工作时，会变得碎片化并失去膜电位，从而导致这些疾病。在这篇综述中，我们探讨了线粒体的融合和裂变过程，特别是在 NDs 背景下。我们讨论了与这些疾病相关的遗传和蛋白质突变，以及它们如何影响线粒体动力学。我们还研究了融合（MFN1、MFN2 和 OPA1）和裂变（DRP1 和 FIS1）中关键的调节蛋白，包括它们的翻译后修饰。此外，我们还强调了可能影响线粒体动力学的潜在药物。通过剖析这些复杂的过程，我们旨在引导研究朝着改善这些具有挑战性疾病患者生活质量的治疗方法发展。
