Skip to Main content Skip to Navigation
Journal articles

FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction

Abstract : The mitochondrial integrated stress response (mitoISR) has emerged as a major adaptive pathway to respiratory chain deficiency, but both the tissue specificity of its regulation, and how mitoISR adapts to different levels of mitochondrial dysfunction are largely unknown. Here, we report that diverse levels of mitochondrial cardiomyopathy activate mitoISR, including high production of FGF21, a cytokine with both paracrine and endocrine function, shown to be induced by respiratory chain dysfunction. Although being fully dispensable for the cell-autonomous and systemic responses to severe mitochondrial cardiomyopathy, in the conditions of mild-to-moderate cardiac OXPHOS dysfunction, FGF21 regulates a portion of mitoISR. In the absence of FGF21, a large part of the metabolic adaptation to mitochondrial dysfunction (one-carbon metabolism, transsulfuration, and serine and proline biosynthesis) is strongly blunted, independent of the primary mitoISR activator ATF4. Collectively, our work highlights the complexity of mitochondrial stress responses by revealing the importance of the tissue specificity and dose dependency of mitoISR.
Document type :
Journal articles
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03639915
Contributor : Marie Lemesle Connect in order to contact the contributor
Submitted on : Wednesday, April 13, 2022 - 11:00:07 AM
Last modification on : Friday, August 5, 2022 - 12:02:55 PM
Long-term archiving on: : Thursday, July 14, 2022 - 6:21:59 PM

File

sciadv.abn7105.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License

Identifiers

Collections

Citation

Marijana Croon, Karolina Szczepanowska, Milica Popovic, Christina Lienkamp, Katharina Senft, et al.. FGF21 modulates mitochondrial stress response in cardiomyocytes only under mild mitochondrial dysfunction. Science Advances , American Association for the Advancement of Science (AAAS), 2022, 8 (14), pp.eabn7105. ⟨10.1126/sciadv.abn7105⟩. ⟨pasteur-03639915⟩

Share

Metrics

Record views

19

Files downloads

122