Molecular regulation of mitochondrial dynamics in cardiac disease.
Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation. By modulating these mitochondrial fission and fusion proteins, mitochondria fine-tune their metabolic status to meet the energy demands of the heart. Moreover, these mitochondrial fission and fusion proteins are essential for mediating mitochondrial autophagy (mitophagy), leading to clearance of damaged mitochondria to maintain a healthy population of mitochondria in heart under stressed conditions. Mitochondrial dynamics dependent improvement in mitochondrial metabolism and quality could partially reverse the pathological conditions of heart. This review describes an overview of mechanisms on mitochondrial dynamics regulation and provides potential therapeutic targets for treating cardiovascular diseases.
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Jinliang
J
Nan
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Wei
W
Zhu
Clinical Research Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
M S
MS
Rahman
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Mingfei
M
Liu
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Dan
D
Li
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Shengan
S
Su
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Na
N
Zhang
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Xinyang
X
Hu
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Hong
H
Yu
Departments of Surgery, Chicago, IL, USA. Electronic address: mgupta@surgery.bsd.uchicago.edu.
Mahesh P
MP
Gupta
Cardiovascular Key Lab of Zhejiang Province, Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: wja@zju.edu.cn.
Jian'an
J
Wang
D000818:Animals; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006331:Heart Diseases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism
D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; D034281:Dynamins
Diabetic cardiomyopathy; Heart failure; Ischemia-reperfusion; Mitochondrial dynamics