Mitochondrial DNA, mitochondrial dysfunction, and cardiac manifestations.
Mitochondria, the powerhouses of cells, have their own DNA (mtDNA). They regulate the transport of metabolites and ions, which determine cell physiology, survival, and death. Mitochondrial dysfunction, including impaired oxidative phosphorylation, preferentially affects heart function via imbalance of energy supply and demand. Recently, mitochondrial mutations and associated mitochondrial dysfunction were suggested as a causal factor of cardiac manifestations. Oxidative stress largely influences mtDNA stability due to oxidative modifications of mtDNA. Furthermore, the continuous replicative state of mtDNA and presence of minimal nucleoid structure render mitochondria vulnerable to oxidative damage and subsequent mutations, which impair mitochondrial functions. However, the occurrence of mtDNA heteroplasmy in the same mitochondrion or cell and presence of nuclear DNA-encoded mtDNA repair systems raise questions regarding whether oxidative stress-mediated mtDNA mutations are the major driving force in accumulation of mtDNA mutations. Here, we address the possible causes of mitochondrial DNA mutations and their involvement in cardiac manifestations. Current strategies for treatment related to mitochondrial mutations and/or dysfunction in cardiac manifestations are briefly discussed.
Department of Integrated Biomedical Science, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Sung Ryul
SR
Lee
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Nari
N
Kim
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Yeonhee
Y
Noh
Department of Physiology and Pathophysiology, Tianjin Medical University, Tainjin 300070, P.R. China.
Zhelong
Z
Xu
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Kyung Soo
KS
Ko
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Byoung Doo
BD
Rhee
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea, phyhanj@inje.ac.kr.
Jin
J
Han
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics*; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008929:Mitochondria, Heart / Q000235:genetics* / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D009154:Mutation; D018384:Oxidative Stress
D004272:DNA, Mitochondrial