Theses and Dissertations


Issuing Body

Mississippi State University


Liu, Bin

Committee Member

Gordon, Donna M.

Committee Member

Lawton, Andrew K

Committee Member

Thornton, Justin A.

Date of Degree


Document Type

Graduate Thesis - Open Access


Biological Sciences

Degree Name

Master of Science (M.S.)


College of Arts and Sciences


Department of Biological Sciences


Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-induced arrhythmia, caused by genetic defects in sarcoplasmic reticulum (SR) Ca-release channel RyR2, or its accessory proteins. Our previous studies demonstrated that CPVT mitochondria can absorb RyR2-mediated aberrant Ca release (ACR) and behave as an efficient Ca buffer which is critical in mitigating harmful consequences of ACR. In this study, we test the hypothesis that modulating mitochondrial phosphate (Pi) transport or the tethering between SR-mitochondria, known as Mitochondria-associated-membrane (MAMs), impacts arrhythmogenesis in CPVT. We found that inhibiting mitochondrial Pi carrier (PiC) exacerbated cellular arrhythmias whereas overexpressing PiC in CPVT alleviated both cellular and in vivo arrhythmias. In parallel, disrupting MAMs exacerbated arrhythmogenesis in CPVT, but promoting MAMs by overexpressing mitofusin2 tethering protein reduced cellular arrhythmias. Our study provided both pharmacological and genetic evidence that directing more Ca to mitochondria by enhancing mitochondrial Pi transport or targeting MAMs could be promising therapeutic strategies to reduce CPVT arrhythmia.

Available for download on Friday, August 15, 2025