Human prohibitin 1 maintains the organization and stability of the mitochondrial nucleoids.
Mitochondrial prohibitin (PHB) proteins have diverse functions, such as the regulation of apoptosis and the maintenance of mitochondrial morphology. In this study, we clarified a novel mitochondrial function of PHB1 that regulates the organization and maintenance of mitochondrial DNA (mtDNA). In PHB1-knockdown cells, we found that mtDNA is not stained by fluorescent dyes, such as ethidium bromide and PicoGreen, although the mitochondrial membrane potential still maintains. We also demonstrated that mtDNA, which is predominantly found in the NP-40-insoluble fraction when isolated from normal mitochondria, is partially released into the soluble fraction when isolated from PHB1-knockdown cells, indicating that the organization of the mitochondrial nucleoids has been altered. Furthermore, we found that PHB1 regulates copy number of mtDNA by stabilizing TFAM protein, a known protein component of the mitochondrial nucleoids. However, TFAM does not affect the organization of mtDNA as observed in PHB1-knockdown cells. Taken together, these results demonstrate that PHB1 maintains the organization and copy number of the mtDNA through both TFAM-independent and -dependent pathways.
Kasashima
Katsumi
K
Department of Biochemistry, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Sumitani
Megumi
M
Satoh
Masaaki
M
Endo
Hitoshi
H
D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D018628:Gene Dosage; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000000981:diagnostic imaging* / Q000235:genetics*; D051336:Mitochondrial Membranes; D024101:Mitochondrial Proteins / Q000502:physiology*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014463:Ultrasonography
D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; C499631:TFAM protein, human; D014157:Transcription Factors