Human Cytochrome C Oxidase Research Articles

Age estimation using cytochrome c oxidase activity analysis

Recently, in the field of forensic medicine the number of unidentified cadavers has increased due to mass disasters and international terrorism. In addition to the conventional anthropological methods, a simple and precise method to estimate the age of these unidentified cadavers to assist in the personal identification is necessary. On the other hand, many researchers have reported that mitochondrial respiratory activity decreases with aging because of the production of reactive oxidative species in the process of ATP generation. Therefore, it may be possible for us to estimate human age by analyzing mitochondrial activity. In this report we attempted to analyze cytochrome c oxidase (CCO) activity, and the amount of protein and mRNA expression in various aged rats. The age of human subjects was estimated through the analysis of human CCO activity from 28 actual forensic cases. The CCO activity, the amount of protein and the mRNA expression increased in the 3rd week and decreased afterwards in rats. Furthermore, human CCO activity was decreased gradually with aging. Therefore, CCO activity analysis may be useful for age estimation in forensic cases.

Studies of COX16, COX19, and PET191 in Human Cytochrome-c Oxidase Deficiency

Cytochrome-c oxidase (COX) is the terminal enzyme of the mitochondrial electron transport chain, and COX deficiency is a common cause of mitochondrial diseases. Cytochrome-c oxidase is composed of 13 subunits, of which 3 are encoded by mitochondrial DNA and 10 by nuclear DNA. Mutations have been identified in each of the 3 mitochondrial DNA genes but in none of the nuclear DNA genes. However, COX deficiency has been attributed to mutations in several nuclear DNA-encoded ancillary proteins needed for COX assembly and function. Despite this progress, the molecular basis of COX deficiency remains elusive in many patients, justifying the identification and screening of additional COX assembly genes, such as COX16, COX19, and PET191. To determine if COX16, COX19, and PET191 are implicated in human COX deficiency. Mutation screening was performed on 53 patients with isolated COX deficiency by direct sequencing of COX19 and by single-strand conformational polymorphism analysis for COX16 and PET191. No mutations were found in COX16, COX19, or PET191 in these patients. The COX16, COX19, and PET191 genes are either not involved or very rarely involved in human COX deficiency. Mutations in additional COX assembly genes remain to be identified.

Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics.

Identifying the genes responsible for human diseases requires combining information about gene position with clues about biological function. The recent availability of whole-genome data sets of RNA and protein expression provides powerful new sources of functional insight. Here we illustrate how such data sets can expedite disease-gene discovery, by using them to identify the gene causing Leigh syndrome, French-Canadian type (LSFC, Online Mendelian Inheritance in Man no. 220111), a human cytochrome c oxidase deficiency that maps to chromosome 2p16-21. Using four public RNA expression data sets, we assigned to all human genes a "score" reflecting their similarity in RNA-expression profiles to known mitochondrial genes. Using a large survey of organellar proteomics, we similarly classified human genes according to the likelihood of their protein product being associated with the mitochondrion. By intersecting this information with the relevant genomic region, we identified a single clear candidate gene, LRPPRC. Resequencing identified two mutations on two independent haplotypes, providing definitive genetic proof that LRPPRC indeed causes LSFC. LRPPRC encodes an mRNA-binding protein likely involved with mtDNA transcript processing, suggesting an additional mechanism of mitochondrial pathophysiology. Similar strategies to integrate diverse genomic information can be applied likewise to other disease pathways and will become increasingly powerful with the growing wealth of diverse, functional genomics data.

Human cytochromec oxidase during cardiac growth and development

Human heart mitochondrial cytochrome c oxidase specific content and specific activity was measured in five fetuses 15-21 weeks gestational age and in five patients whose age ranged from 6 days to 22 years. None had evidence of cardiac pathology. An increase in cytochrome c oxidase specific content and specific activity was observed in the fetal heart with increasing gestational age (0.13-0.38 nmol heme a/mg protein and 67-295 nmol O2 utilized/min/mg protein) and from the neonatal period (0.35 nmol heme a/mg protein and 140 nmol O2/min/mg protein) to adulthood (1.2 nmol heme a/mg protein and 1104 nmol O2/min/mg protein). A marked increase was observed postnatally between 4 and 19 months.