APA
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Walker, E., Pearson, G. L., Lawlor, N., Stendahl, A. M., Lietzke, A., Sidarala, V., … Soleimanpour, S. (2025). Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues. Science.
Chicago/Turabian
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Walker, E., Gemma L. Pearson, Nathan Lawlor, Ava M. Stendahl, Anne Lietzke, Vaibhav Sidarala, Jie Zhu, et al. “Retrograde Mitochondrial Signaling Governs the Identity and Maturity of Metabolic Tissues.” Science (2025).
MLA
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Walker, E., et al. “Retrograde Mitochondrial Signaling Governs the Identity and Maturity of Metabolic Tissues.” Science, 2025.
BibTeX Click to copy
@article{e2025a,
title = {Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.},
year = {2025},
journal = {Science},
author = {Walker, E. and Pearson, Gemma L. and Lawlor, Nathan and Stendahl, Ava M. and Lietzke, Anne and Sidarala, Vaibhav and Zhu, Jie and Stromer, Tracy and Reck, Emma C. and Li, Jin and Levi-D'Ancona, Elena and Pasmooij, Mabelle B. and Hubers, Dre L and Renberg, Aaron and Mohamed, Kawthar and Parekh, V. and Zhang, Irina X. and Thompson, B. and Zhang, Deqiang and Ware, Sarah A. and Haataja, L. and Qi, Nathan R. and Parker, Stephen C. J. and Arvan, P. and Yin, L. and Kaufman, B. and Satin, L. and Sussel, L. and Stitzel, M. and Soleimanpour, S.}
}
Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences of compromised mitochondria in metabolic tissues are often unclear. Here, we report that dysfunctional mitochondrial quality control engages a retrograde (mitonuclear) signaling program that impairs cellular identity and maturity in β-cells, hepatocytes, and brown adipocytes. Targeted deficiency throughout the mitochondrial quality control pathway, including genome integrity, dynamics, or turnover, impaired the oxidative phosphorylation machinery, activating the mitochondrial integrated stress response, eliciting chromatin remodeling, and promoting cellular immaturity rather than apoptosis to yield metabolic dysfunction. Indeed, pharmacologic blockade of the integrated stress response in vivo restored β-cell identity following loss of mitochondrial quality control. Targeting mitochondrial retrograde signaling may therefore be promising in the treatment or prevention of metabolic disorders.