Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders and have been found to accumulate during normal aging. Despite the fact that hundreds of deletions have been characterized at the molecular level, their mechanisms of genesis are unknown. We tested the effect of double-strand breaks of muscle mtDNA by developing a mouse model in which a mitochondrially targeted re...

The effect of temperature on the activation energies of mitochondrial enzymes of the yeast Saccharomyces cerevisiae was examined. Non-linear Arrhenius plots with discontinuities in the temperature range 14-19 degrees C and 19-22 degrees C were observed for the respiratory enzymes and mitochondrial ATPase (adenosine triphosphatase) respectively. A straight-line Arrhenius plot was observed for th...

Using a computational model, we simulated mitochondrial deoxynucleotide metabolism and mitochondrial DNA replication. Our results indicate that the output from the mitochondrial salvage enzymes alone is inadequate to support a mitochondrial DNA replication duration of as long as 10 hours. We find that an external source of deoxyribonucleoside diphosphates or triphosphates (dNTPs), in addition t...

AIMS Sarco(endo)plasmic reticulum Ca²(+)-ATPase 2a (SERCA2a) transports Ca²(+) by consuming ATP produced by mitochondrial respiratory chain enzymes. Messenger RNA (mRNA) for these enzymes is transcribed by mitochondrial transcription factors A (TFAM) and B2 (TFB2M). This study examined whether TFAM and TFB2M coordinately regulate the transcription of the Serca2 gene and mitochondrial genes. M...

OBJECTIVE Mitochondrial dysfunctions, impaired bioenergetics and dysfunction of neurotrophins are included in many neurodegenerative and psychiatric diseases. We investigated in vitro effects of pharmacologically different antidepressants and mood stabilizers on mitochondrial enzymes to discover, which mitochondrial functions could be involved in pathophysiology of mood disorders. METHODS In ...

Mitochondrial cytochromes P450 presumably originated from a common microsomal ancestor. However, it is still unknown how ancient mitochondrial P450s were able to retain their oxygenase function following relocation the matrix and later emerged as enzymes specialized for steroid hormone biosynthesis in vertebrates. Here, we used approach of ancestral sequence reconstruction (ASR) resurrect CYP11...

Four cytoplasmically synthesized rat liver mitochondrial enzymes, located either as soluble enzymes in the mitochondrial matrix (L-glutamate dehydrogenase and malate dehydrogenase or in the intermembrane space (sulfite oxidase) or as an integral membrane protein located on the matrix face of the inner mitochondrial membrane (D-beta-hydroxybutyrate dehydrogenase), were all shown to be synthesize...

Mitochondria contain more than 1000 different proteins, including several proteolytic enzymes. These mitochondrial proteases form a complex system that performs limited and terminal proteolysis to build the proteome, maintain, control its functions or degrade proteins peptides. During protein biogenesis, presequence cleave targeting signals obtain mature functional proteins. Processing by also ...

The anaerobic chytrid Piromyces sp. E2 lacks mitochondria, but contains hydrogen-producing organelles, the hydrogenosomes. We are interested in how the adaptation to anaerobiosis influenced enzyme compartmentalization in this organism. Random sequencing of a cDNA library from Piromyces sp. E2 resulted in the isolation of cDNAs encoding malate dehydrogenase, aconitase and acetohydroxyacid reduct...