Bergami Matteo, Motori Elisa
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Cologne, Germany.
Institute of Genetics, University of Cologne, Cologne, Germany.
Front Cell Dev Biol. 2020 Oct 23;8:592651. doi: 10.3389/fcell.2020.592651. eCollection 2020.
The endoplasmic reticulum (ER) and mitochondria are classically regarded as very dynamic organelles in cell lines. Their frequent morphological changes and repositioning underlie the transient generation of physical contact sites (so-called mitochondria-ER contacts, or MERCs) which are believed to support metabolic processes central for cellular signaling and function. The extent of regulation over these organelle dynamics has likely further achieved a higher level of complexity in polarized cells like neurons and astrocytes to match their elaborated geometries and specialized functions, thus ensuring the maintenance of MERCs at metabolically demanding locations far from the soma. Yet, live imaging of adult brain tissue has recently revealed that the true extent of mitochondrial dynamics in astrocytes is significantly lower than in cell culture settings. On one hand, this suggests that organelle dynamics in mature astroglia may be highly regulated and perhaps triggered only by defined physiological stimuli. On the other hand, this extent of control may greatly facilitate the stabilization of those MERCs required to maintain regionalized metabolic domains underlying key astrocytic functions. In this perspective, we review recent evidence suggesting that the resulting spatial distribution of mitochondria and ER in astrocytes may create the conditions for maintaining extensive MERCs within specialized territories - like perivascular endfeet - and discuss the possibility that their enrichment at these distal locations may facilitate specific forms of cellular plasticity relevant for physiology and disease.
内质网（ER）和线粒体在细胞系中传统上被视为非常动态的细胞器。它们频繁的形态变化和重新定位是物理接触位点（所谓的线粒体-内质网接触，或MERCs）短暂产生的基础，据信这些接触位点支持细胞信号传导和功能的核心代谢过程。在神经元和星形胶质细胞等极化细胞中，对这些细胞器动态的调控程度可能进一步达到了更高的复杂程度，以匹配它们精细的几何形状和特殊功能，从而确保在远离胞体的代谢需求部位维持MERCs。然而，最近对成体脑组织的活体成像显示，星形胶质细胞中线粒体动态的真实程度明显低于细胞培养环境。一方面，这表明成熟星形胶质细胞中的细胞器动态可能受到高度调控，或许仅由特定的生理刺激触发。另一方面，这种控制程度可能极大地促进维持关键星形胶质细胞功能基础的区域化代谢域所需的那些MERCs的稳定。从这个角度来看，我们回顾了最近的证据，这些证据表明星形胶质细胞中线粒体和内质网的空间分布可能为在特殊区域（如血管周围终足）内维持广泛的MERCs创造条件，并讨论它们在这些远端位置富集可能促进与生理和疾病相关的特定形式细胞可塑性的可能性。
