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#CellBiology #Immunology #Metabolism #Mitochondria #IronMetabolism #Homeostasis #OpenScience
(9/9)

Thanks to @gimmfoundation.bsky.social, specially Rui Martins and Birte Blankehaus for leading this work. David Sancho @sancholab.bsky.social and Stefanie Wculek @swculek.bsky.social for critical mouse models (TFAM and UQCRQ deletions) that unlocked the mitochondrial biogenesis mechanism!
(8/9)

This work reveals macrophages as "ferrostats" - sensing iron dysregulation and cross-regulating iron and energy metabolism. Metchnikoff's vision of macrophages as central homeostatic regulators extends beyond immunity to fundamental control of organismal metabolism.
(7/9)

The impact is profound: FTH-competent macrophages rescued mice from lethal metabolic collapse, restoring cardiac function, thermogenesis, and energy balance. They're not just immune cells - they're metabolic orchestrators maintaining whole-body homeostasis.
(6/9)

This "transmitophagy" allows damaged tissues to outsource the energetically demanding process of clearing dysfunctional mitochondria. Macrophages act as cellular recycling centers - but only if they express FTH to handle the iron load from incoming mitochondria.
(5/9)

Here's the surprising part: we discovered intercellular mitochondrial transfer - but in the OPPOSITE direction of what we expected! Stressed parenchymal cells transfer their dysfunctional mitochondria TO macrophages, not the other way around.
(4/9)

How do macrophages "know" tissues are in trouble? They detect mitochondrial dysfunction in stressed parenchymal cells. In response, FTH-competent macrophages activate a unique transcriptional program centered on mitochondrial biogenesis, controlled by TFAM.
(3/9)

When we deleted ferritin (FTH) - the master iron storage protein - in mouse tissues, something remarkable happened: monocyte-derived macrophages sensed this disruption and mounted a rescue response to restore energy metabolism and prevent organ failure.
(2/9)

of the influenza vaccine is low (against infection). What is forgotten is the protection from non-communicable diseases.

What if you could reduce your risk to heart disease by 40%?
What is you could reduce you risk to dementia by at least 10%?

That is what vaccines do!
3/10

Obrigado!

Could have not said it better!