We already knew that microglial activation induces mitochondrial fragmentation and that mito morphology correlates with its Ca2+ uptake
But the influence of mito Ca2+ handling on #microglial activation was still unclear...
3/11
Here, LPS-activation of BV-2 #microglia decreased both mitochondrial Ca2+ retention capacity and uptake rate.
These mitochondria were more fragmented, less polarized and and showed decreased respiratory control.
4/11
And more: LPS-activation also depleted ER Ca2+ stores and impaired SOCE (store-operated calcium entry).
Alright, this could be a pretty expected effect for LPS...but as we say in 🇧🇷: "AÍ É QUE TÁ!"
What if we could play with that?🥸
5/11
Our group had recently shown that genetic manipulation of mitochondrial dynamics can directly regulate mitochondrial Ca2+ uptake, thus affecting Ca2+ homeostasis
Induction of mitochondrial fragmentation perfectly mimicked LPS effect on SOCE and ER Ca2+ depletion 👌
7/11
The coolest part? Avoiding mito fragmentation was sufficient to protect cells from this very same phenotype!
This reinforces the importance of the interplay between mito morphology / ion transport / Ca2+ homeostasis on microglial LPS-activation
8/11
While we are still not sure how this type of modulation influences microglial functions, "this was a novel aspect of cell signaling observed during microglial activation, which may be central toward the role of these cells in inflammation"
9/11 link.springer.com/article/10.100…
A simple, direct approach created a nice story. Kudos to everyone that made it possible!
@osvaldo_rpe, @VITORDEMIRANDA3 and our mentor @AJKowaltowski (which granted me the amazing opportunity of working in this project and to share the co-corresponding position)
10/11
Ah, the paper's PDF can also be accessed through this link (in case your institution does not cover @SpringerNature's Journal of Bioenergetics and Biomembranes subscription):