Characterization of endonuclease G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy.
Endonuclease G (Endo G) is a novel determinant of cardiac hypertrophy. Here, we report the characterization of Endo G and mitochondria-sarcoplasmic reticulum-related proteins during cardiac hypertrophy, and hypothesize that Endo G regulate mitochondrial function partly through Mfn2 and Jp2 during cardiac hypertrophy. Our results show that Endo G levels gradually increased at the beginning of phenylephrine-induced cardiac hypertrophy, accompanied by an abnormal mitochondrial membrane potential. The up-regulation of Mfn2, Jp2, and Endo G appeared at an early stage of cardiac hypertrophy, whereas PGC1α was not up-regulated until a later stage. Abolishing Endo G with siRNA led to the uncoupling of the mitochondrial electron transport chain from ATP production and decreased PGC1α expression, likely by affecting the juxtaposition of the mitochondria and the sarcoplasmic reticulum via Mfn2 and Jp2. Furthermore, abolishing Jp2 altered the expression of Endo G expression and induced mitochondrial dysfunction, suggesting that mitochondrial abnormalities in cardiac hypertrophy are most likely caused by Endo G. Taken together, our study established a link between Endo G and mitochondrial function during cardiac hypertrophy, partly through the effects of Endo G on Mfn2 and Jp2, and revealed a role for Endo G in the crosstalk between the processes controlled by Mfn2 and Jp2 in maladaptive cardiac hypertrophy.
Xingguang
X
Liang
Kuifen
K
Ma
Yuefeng
Y
Rao
Dongsheng
D
Hong
Zhaoxia
Z
Huo
Ziqi
Z
Ye
Mingzhu
M
Huang
Xingguo
X
Zhang
Qingwei
Q
Zhao
D015415:Biomarkers; D006332:Cardiomegaly / Q000378:metabolism*; D002460:Cell Line; D004706:Endodeoxyribonucleases / Q000032:analysis* / Q000235:genetics; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D008929:Mitochondria, Heart / Q000737:chemistry* / Q000235:genetics; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics; D032383:Myocytes, Cardiac / Q000201:enzymology; D034741:RNA, Small Interfering / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000737:chemistry* / Q000235:genetics
D015415:Biomarkers; C000589041:JPH2 protein, human; D008565:Membrane Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D004706:Endodeoxyribonucleases; C052391:endonuclease G