Communications Biology · 10 authors, 10 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
The study generated transgenic mice with systemic overexpression of two different citrate transporters. While both increased cytosolic citrate and acetyl-CoA, only SLC13A5 overexpression caused a progeria-like phenotype and premature death, linked to increased engagement of the ER acetylation machinery.
This preclinical study generated transgenic mice with systemic overexpression (sTg) of either SLC25A1 or SLC13A5, which import cytosolic citrate from the mitochondria and extracellular space, respectively. Both models showed increased cytosolic citrate and acetyl-CoA levels. However, SLC13A5 sTg mice developed a progeria-like phenotype with premature death, while SLC25A1 sTg mice did not. Metabolic profiling revealed widespread differences, and SLC13A5 sTg mice displayed increased engagement of the endoplasmic reticulum (ER) acetylation machinery via SLC33A1, unlike SLC25A1 sTg mice. The findings suggest that the directionality and source of citrate flux, not just metabolite levels, can transduce different biological signals.
