title: Mitochondrial DNA, mitochondrial dysfunction, and cardiac manifestations.
abstract: Mitochondria, are the powerhouses of cells, have their own DNA (mtDNA), regulate the transport of metabolites and ions, and impact cell physiology, survival, and death. Mitochondrial dysfunction, including impaired oxidative phosphorylation, preferentially affects heart function due to an 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.
authors.affiliation: Department of Integrated Biomedical Science, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Sung Ryul
authors.initials: SR
authors.lastname: Lee
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Yeun Hee
authors.initials: YH
authors.lastname: Noh
authors.affiliation: Department of Physiology and Pathophysiology, Tianjin Medical University, Tainjin 300070, P.R. China.
authors.forename: Zhelong
authors.initials: Z
authors.lastname: Xu
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Ko
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
authors.forename: Byoung Doo
authors.initials: BD
authors.lastname: Rhee
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea, Jin Han phyhanj@inje.ac.kr.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism*; D006331:Heart Diseases / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008929:Mitochondria, Heart / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D009154:Mutation; D018384:Oxidative Stress
chemical_list: D004272:DNA, Mitochondrial