title: Low abundance of mitochondrial DNA changes mitochondrial status and renders cells resistant to serum starvation and sodium nitroprusside insult.
abstract: Mutation or depletion of mitochondrial DNA (mtDNA) can cause severe mitochondrial malfunction, originating from the mitochondrion itself, or from the crosstalk between nuclei and mitochondria. However, the changes that would occur if the amount of mtDNA is diminished are less known. Thus, we generated rat myoblast H9c2 cells containing lower amounts of mtDNA via ethidium bromide and uridine supplementation. After confirming the depletion of mtDNA by quantitative PCR and gel electrophoresis analysis, we investigated the changes in mitochondrial physical parameters by using flow cytometry. We also evaluated the resistance of these cells to serum starvation and sodium nitroprusside. H9c2 cells with diminished mtDNA contents showed decreased mitochondrial membrane potential, mass, free calcium, and zinc ion contents as compared to naïve H9c2 cells. Furthermore, cytosolic and mitochondrial reactive oxygen species levels were significantly higher in mtDNA-lowered H9c2 cells than in the naïve cells. Although the oxygen consumption rate and cell proliferation were decreased, mtDNA-lowered H9c2 cells were more resistant to serum deprivation and nitroprusside insults than the naïve H9c2 cells. Taken together, we conclude that the low abundance of mtDNA cause changes in cellular status, such as changes in reactive oxygen species, calcium, and zinc ion levels inducing resistance to stress.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of 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, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Heo
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jeong
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of Korea.
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of Korea.
authors.forename: In Sung
authors.initials: IS
authors.lastname: Song
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of 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, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of 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, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of 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, Bokji-Ro 75, Busanjin-gu, Busan, 614 735, Republic of Korea.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D017382:Reactive Oxygen Species; D044967:Serum / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D009599:Nitroprusside
keywords: H9c2; abundance; copy number; mitochondrial DNA; resistance