Loss of Mitochondrial Ca2+ Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy.
Edoardo BerteroAlexander NickelMichael KohlhaasMathias HohlVasco SequeiraCarolin BruneJulia SchwemmleinMarco AbeßerKai SchuhIlona KutschkaChristopher CarleinKai MünkerSarah AtighetchiAndreas MüllerAndrey KazakovReinhard KapplKarina von der MalsburgMartin van der LaanAnna-Florentine SchiumaMichael BöhmUlrich LaufsMarkus HothPeter RehlingMichaela KuhnJan DudekAlexander von der MalsburgLeticia Prates RomaChristoph MaackPublished in: Circulation (2021)
Downregulation of mitochondrial Ca2+ uniporter, increased myofilament Ca2+ affinity, and preactivated sarcoplasmic reticulum Ca2+-ATPase provoke mechano-energetic uncoupling that explains diastolic dysfunction and the lack of inotropic reserve in BTHS cardiomyopathy. Furthermore, defective mitochondrial Ca2+ uptake provides a trigger and a substrate for ventricular arrhythmias. These insights can guide the ongoing search for a cure of this orphaned disease.