Coordinated metabolic responses to cyclophilin D deletion in the developing heart.

Autor:	Beutner G; Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center, Rochester, NY 14642, USA., Burris JR; Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center, Rochester, NY 14642, USA.; Department of Pediatrics, Division of Neonatology, University of Rochester Medical Center, Rochester, NY 14642, USA., Collins MP; Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center, Rochester, NY 14642, USA., Kulkarni CA; Department of Anesthesiology & Perioperative Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA., Nadtochiy SM; Department of Anesthesiology & Perioperative Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA., de Mesy Bentley KL; Department of Pathology & Laboratory Medicine and the Electron Microscope Resource, University of Rochester Medical Center, Rochester, NY 14642, USA., Cohen ED; Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center, Rochester, NY 14642, USA., Brookes PS; Department of Anesthesiology & Perioperative Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA., Porter GA Jr; Department of Pediatrics, Division of Cardiology, University of Rochester Medical Center, Rochester, NY 14642, USA.; Departments of Medicine (Aab Cardiovascular Research Institute) and Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Feb 09; Vol. 27 (3), pp. 109157. Date of Electronic Publication: 2024 Feb 09 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109157
Abstrakt:	In the embryonic heart, the activation of the mitochondrial electron transport chain (ETC) coincides with the closure of the cyclophilin D (CypD) regulated mitochondrial permeability transition pore (mPTP). However, it remains to be established whether the absence of CypD has a regulatory effect on mitochondria during cardiac development. Using a variety of assays to analyze cardiac tissue from wildtype and CypD knockout mice from embryonic day (E)9.5 to adult, we found that mitochondrial structure, function, and metabolism show distinct transitions. Deletion of CypD altered the timing of these transitions as the mPTP was closed at all ages, leading to coupled ETC activity in the early embryo, decreased citrate synthase activity, and an altered metabolome particularly after birth. Our results suggest that manipulating CypD activity may control myocyte proliferation and differentiation and could be a tool to increase ATP production and cardiac function in immature hearts. Competing Interests: GAPJr is the Inventor and the University of Rochester is the Assignee of United States Patent No. “US 10,179,161 B2” dated 1/15/19 and entitled “Compositions and methods for enhancing cardiac function in the neonate” that is related to the work reported herein. All other authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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