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

Author(s)

Pereira Jr, O. R. ; Ramos, V. M. ^[1] ; Cabral-Costa, J. V. ^[1] ; Kowaltowski, A. J. ^[1]

Affiliation

^[1] Pereira Jr, Jr., O. R., Univ Sao Paulo, Inst Quim, Dept Bioquim, Ave Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Journal of Bioenergetics and Biomembranes; v. 53, n. 2, p. 109-118, APR 2021.
• Web of Science Citations: 0

Abstract

Microglial activation involves both fragmentation of the mitochondrial network and changes in cellular Ca2+ 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 Ca2+ homeostasis in microglial cells, a new aspect of microglial activation that could be a key feature in the inflammatory role of these cells. (AU)

• FAPESP's process: 19/18402-4 - Effects of mitochondrial calcium transport regulation in autophagic process of hepatocytes
• Grantee: Vitor de Miranda Ramos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/22178-2 - NCLX in astrocytic function: metabolism and neuronal homeostasis
• Grantee: João Victor Cabral Costa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 20/06970-5 - Mitochondrial ion transporters as sensors and regulators in energy metabolism
• Grantee: Alicia Juliana Kowaltowski
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/14713-0 - Mitochondrial Ca2+ Handling in the Central Nervous System and Energy Metabolism Regulation
• Grantee: João Victor Cabral Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/21487-9 - Evaluation of NCLX and MCU functions in the central nervous system
• Grantee: Osvaldo Rodrigues Pereira Junior
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC