Protein kinase D activation induces mitochondrial fragmentation and dysfunction in cardiomyocytes

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12793-list-0001">Abnormal mitochondrial morphology and function in cardiomyocytes are frequently observed under persistent Gq protein‐coupled receptor (GqPCR) stimulation.Cardiac signalling mechanisms for regulating mitochondrial morphology and function under pathophysiological conditions in the heart are still poorly understood.We demonstrate that a downstream kinase of GqPCR, protein kinase D (PKD) induces mitochondrial fragmentation via phosphorylation of dynamin‐like protein 1 (DLP1), a mitochondrial fission protein.The fragmented mitochondria enhance reactive oxygen species generation and permeability transition pore opening in mitochondria, which initiate apoptotic signalling activation.This study identifies a novel PKD‐specific substrate in cardiac mitochondria and uncovers the role of PKD on cardiac mitochondria, with special emphasis on the molecular mechanism(s) underlying mitochondrial injury with abnormal mitochondrial morphology under persistent GqPCR stimulation.These findings provide new insights into the molecular basis of cardiac mitochondrial physiology and pathophysiology, linking GqPCR signalling with the regulation of mitochondrial morphology and function.