Coordinated Metabolic Responses to Cyclophilin D Deletion in the Developing Heart

Overview

Journal iScience

Publisher Cell Press

Date 2024 Feb 28

PMID 38414851

Authors

Gisela Beutner

Jonathan Ryan Burris

Michael P Collins

Chaitanya A Kulkarni

Sergiy M Nadtochiy

Karen L de Mesy Bentley

Ethan D Cohen

Paul S Brookes

George A Porter Jr

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

N-terminal cleavage of cyclophilin D boosts its ability to bind F-ATP synthase.

Coluccino G, Negro A, Filippi A, Bean C, Muraca V, Gissi C Commun Biol. 2024; 7(1):1486.

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The multifaceted role of mitochondria in cardiac function: insights and approaches.

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