Mitochondrial nucleic acid binding proteins associated with diseases.
Mammalian mitochondrial DNA (mtDNA) exists in structures called nucleoids, which correspond to the configuration of nuclear DNA. Mitochondrial transcription factor A (TFAM), first cloned as an mtDNA transcription factor, is critical for packaging and maintaining mtDNA. To investigate functional aspects of TFAM, we identified many RNA-binding proteins as candidate TFAM interactors, including ERAL1 and p32. In this review, we first describe the functions of TFAM, replication proteins such as polymerase gamma and Twinkle, and mitochondrial RNA binding proteins. We describe the role of mitochondrial nucleic acid binding proteins within the mitochondrial matrix and two oxidative phosphorylation-related proteins within the mitochondrial intermembrane space. We then discuss how mitochondrial dysfunction is related to several diseases, including mitochondrial respiratory disease, Miller syndrome and cancer. We also describe p32 knockout mice, which are embryonic lethal and exhibit respiratory chain defects. Miller syndrome is a recessive disorder characterized by postaxial acrofacial dysostosis and caused by a mutation inDHODH. Finally, we explain that p32 and mitochondrial creatine kinase may be novel markers for the progression of prostate cancer.
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan, uchiumi@cclm.med.kyushu-u.ac.jp.
Takeshi
T
Uchiumi
Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Dongchon
D
Kang
D000015:Abnormalities, Multiple / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D000074002:DNA Polymerase gamma / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000378:metabolism; D008342:Mandibulofacial Dysostosis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008844:Micrognathism / Q000235:genetics / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043262:Ribonuclease P / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C087299:C1QBP protein, human; D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; C087940:LRPPRC protein, human; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; D000074002:DNA Polymerase gamma; C413027:POLG protein, human; D043262:Ribonuclease P; C552417:ERAL1 protein, human; D019204:GTP-Binding Proteins; D004265:DNA Helicases; C431576:TWNK protein, human