RT Journal Article
T1 Ferritin regulates organismal energy balanceand thermogenesis
A1 Blankenhaus, Birte
A1 Braza, Faouzi
A1 Martins, Rui
A1 Bastos Amador, Patricia
A1 González García, Ismael
A1 Carlos, Ana Rita
A1 Mahu, Inês
A1 Faisca, Pedro
A1 Moura Nunes, Jose
A1 Ventura, Pedro
A1 Hoerr, Verena
A1 Weis, Sebastian
A1 Guerra, Joel
A1 Cardoso, Silvia
A1 Domingos, Ana I.
A1 López Pérez, Miguel A.
A1 Soares, Miguel P.
K1 Iron metabolism
K1 Redox homeostasis
K1 Adipose tissue
K1 Energy expenditure
K1 Mitochondria
AB [ENG]Objective:The ferritin heavy/heart chain (FTH) gene encodes the ferroxidase component of the iron (Fe) sequestering ferritin complex, whichplays a central role in the regulation of cellular Fe metabolism. Here we tested the hypothesis that ferritin regulates organismal Fe metabolism in amanner that impacts energy balance and thermal homeostasis.Methods:We developed a mouse strain, referred herein asFthR26fl/fl, expressing a tamoxifen-inducible Cre recombinase under the control of theRosa26(R26) promoter and carrying two LoxP (fl) sites: one at the 50end of theFthpromoter and another the 3’end of thefirstFthexon.Tamoxifen administration induces global deletion ofFthin adultFthR26D/Dmice, testing whether FTH is required for maintenance of organismalhomeostasis.Results:Under standard nutritional Fe supply,Fthdeletion in adultFthR26D/Dmice led to a profound deregulation of organismal Fe metabolism,oxidative stress, inflammation, and multi-organ damage, culminating in death. Unexpectedly,Fthdeletion was also associated with a profoundatrophy of white and brown adipose tissue as well as with collapse of energy expenditure and thermogenesis. This was attributed mechanisticallyto mitochondrial dysfunction, as assessed in the liver and in adipose tissue.Conclusion:The FTH component of ferritin acts as a master regulator of organismal Fe homeostasis, coupling nutritional Fe supply to organismalredox homeostasis, energy expenditure and thermoregulation
PB Elsevier
SN 2212-8778
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21497
UL http://hdl.handle.net/10347/21497
LA eng
NO Blankenhaus, B., Braza, F., Martins, R., Bastos-Amador, P., González-García, I., & Carlos, A. et al. (2019). Ferritin regulates organismal energy balance and thermogenesis. Molecular Metabolism, 24, 64-79. doi: 10.1016/j.molmet.2019.03.008
NO MPS is supported by Fundação Calouste Gulbenkian and by Fundação para aCiênciaeaTecnologia,Portugal(PTDC/IMI-IMU/5723/2014 and 02/SAICT/2017).FCT support to ARC (SFRH/BPD/101608/2014) and PBA (PTDC/IMI-IMU/5723/2014) is acknowledged. BB and SC were supported in part by European Community7th Framework 294709-DAMAGECONTROL ERC-2011-AdG to MPS, FB by MarieSkłodowska-Curie Research Fellowship (REGDAM 707998), RM by EMBO long-term fellowship (ALTF 290-2017), ML by Xunta de Galicia (2015-CP079) andMINECO from EU FEDER Program (SAF2015-71026-R), SW and JG by the GermanMinistry of Education and Research (BMBF; grant 01 EO 1502) via the Jena Centerof Sepsis Control and Care
DS Minerva
RD 27 abr 2026