Changes in mitochondrial morphology modulate LPS-induced loss of calcium homeostasis in BV-2 microglial cells

• Published in: Journal of bioenergetics and biomembranes Vol. 53; no. 2; pp. 109 - 118
• Main Authors: Pereira, O. R., Ramos, V. M., Cabral-Costa, J. V., Kowaltowski, A. J.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2021; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Biochemistry; Bioorganic Chemistry; Calcium; Calcium (mitochondrial); Calcium - metabolism; Calcium homeostasis; Calcium influx; Calcium ions; Calcium signalling; Cell activation; Cellular communication; Chemistry; Chemistry and Materials Science; Cytology; Fragmentation; Histology; Homeostasis; Homeostasis - immunology; Humans; Inflammation; Lipopolysaccharides; Lipopolysaccharides - metabolism; Membrane potential; Microglia; Microglia - metabolism; Mitochondria; Mitochondria - metabolism; Morphology; Organic Chemistry; Replenishment; Retention capacity; Inflammation; Calcium handling; Metabolism; Mitochondrial morphology
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-021-09878-4

Microglial activation involves both fragmentation of the mitochondrial network and changes in cellular Ca
2+
homeostasis, but possible modifications in mitochondrial calcium uptake have never been described in this context. Here we report that activated microglial BV-2 cells have impaired mitochondrial calcium uptake, including lower calcium retention capacity and calcium uptake rates. These changes were not dependent on altered expression of the mitochondrial calcium uniporter. Respiratory capacity and the inner membrane potential, key determinants of mitochondrial calcium uptake, are both decreased in activated microglial BV-2 cells. Modified mitochondrial calcium uptake correlates with impaired cellular calcium signaling, including reduced ER calcium stores, and decreased replenishment by store operated calcium entry (SOCE). Induction of mitochondrial fragmentation through Mfn2 knockdown in control cells mimicked this effect, while inhibiting LPS-induced mitochondrial fragmentation by a dominant negative form of Drp1 prevented it. Overall, our results show that mitochondrial fragmentation induced by LPS promotes altered Ca
2+
homeostasis in microglial cells, a new aspect of microglial activation that could be a key feature in the inflammatory role of these cells.