Astrocytes shed large membrane vesicles that contain mitochondria, lipid droplets and ATP

Abstract

Various cells types, including stem and progenitor cells, can exchange complex information via plasma membrane-derived vesicles, which can carry signals both in their limiting membrane and lumen. Astrocytes, traditionally regarded as mere supportive cells, play previously unrecognized functions in neuronal modulation and are capable of releasing signalling molecules of different functional significance. In the present study, we provide direct evidence that human fetal astrocytes in culture, expressing the same feature as immature and reactive astrocytes, release membrane vesicles larger than the microvesicles described up to now. We found that these large vesicles, ranging from 1-5 to 8 μm in diameter and expressing on their surface β1-integrin proteins, contain mitochondria and lipid droplets together with ATP. We documented vesicle content with fluorescent-specific dyes and with the immunocytochemistry technique we confirmed that mitochondria and lipid droplets were co-localized in the same vesicle. Scanning electron microscopy and transmission electron microscopy confirmed that astrocytes shed from surface membrane vesicles of the same size as the ones detected by fluorescence microscopy. Our results report for the first time that cultured astrocytes, activated by repetitive stimulation of ATP released from neighboring cells, shed from their surface large membrane vesicles containing mitochondria and lipid droplets.

Transfer of mitochondria from astrocytes to neurons after stroke

“…Images were collected using an AMT digital imaging system (Advanced Microscopy Techniques, Danvers, MA). These methods are similar to previous descriptions of extracellular particle and mitochondria detection in astrocyte cultures 12 .…”

“…Healthy mitochondria may be essential for these neuroglial protective mechanisms because inhibition of astrocytic mitochondria makes neurons vulnerable to cell death 10 . Mitochondria comprise the intracellular cores for energetics and viability 11 , but under some conditions mitochondria might also be released into extracellular space 12 . For instance, retinal neurons may transfer mitochondria to astrocytes for disposal and recycling 1 , and bone-marrow derived stromal cells may transfer mitochondria into pulmonary alveoli to suppress acute lung injury 13 .…”

17β-estradiol regulates giant vesicle formation via estrogen receptor-alpha in human breast cancer cells

“…These vesicles were shown to contain bioactive matrix metalloproteinases (MMP2 and MMP9), enzymes that have critical importance in tumour invasion, in addition to RNA, ADP-ribosylation factor 6 and caveolin-1. Additional evidence for the existence of extracellular vesicles larger than submicron diameter microvesicles is also provided by the recent identification of extracellular vesicles up to 8μm in diameter produced by astrocytes [37]. …”

Mechanisms of Neurovascular Dysfunction in Acute Ischemic Brain

“…But they also shed ECVs that may induce angiogenesis and apoptosis [118, 119]. Within larger ECVs shed from astrocytes, mitochondria and other membranous organelles were identified [120]. Oligodendrocytes also secrete exosomes to balance myelin proteins and lipids and to relieve cell stress.…”