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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Pereira Jr, O. R. ; Ramos, V. M. [1] ; Cabral-Costa, J. V. [1] ; Kowaltowski, A. J. [1]
Total Authors: 4
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
Total Affiliations: 1
Document type: Journal article
Source: Journal of Bioenergetics and Biomembranes; v. 53, n. 2 FEB 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: 20/06970-5 - Mitochondrial ion transporters as sensors and regulators in energy metabolism
Grantee:Alicia Juliana Kowaltowski
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 19/18402-4 - Effects of mitochondrial calcium transport regulation in autophagic process of hepatocytes
Grantee:Vitor de Miranda Ramos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/14713-0 - Mitochondrial Ca2+ Handling in the Central Nervous System and Energy Metabolism Regulation
Grantee:João Victor Cabral Costa
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 19/22178-2 - NCLX in astrocytic function: metabolism and neuronal homeostasis
Grantee:João Victor Cabral Costa
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 18/21487-9 - Evaluation of NCLX and MCU functions in the central nervous system
Grantee:Osvaldo Rodrigues Pereira Junior
Support type: Scholarships in Brazil - Scientific Initiation