Mitochondrial DNA haplogroups and serum levels of proteolytic enzymes in patients with osteoarthritis.

in Annals of the Rheumatic Diseases (2011), 70(4), 646-52

OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). METHODS: Serum levels ... [more ▼]

OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). METHODS: Serum levels of metalloproteinase-1 (MMP-1), MMP-3, MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and 77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from grade 0 to grade IV. Non-parametric and multiple regression analyses were performed to test the effects of clinical variables, including gender, age, smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels of these enzymes. RESULTS: A significant influence of the haplogroups on the serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035, respectively). Patients with OA with haplogroup H showed higher serum levels of MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels than H carriers. Besides, levels of MMP-13 were proportionally higher in radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A (K/L grade 0 and I) (p=0.005). CONCLUSIONS: This study shows that haplogroups have a significant influence on serum levels of MMP-3 and MMP-13. The influence of the haplogroups on serum levels of MMP-3 is clearly dependent on the diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is independent of diagnosis. [less ▲]

Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs.

in Neurology (2009), 72(18), 1588-94

OBJECTIVES: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the ... [more ▼]

OBJECTIVES: In migraine, an interictal reduction of mitochondrial energy metabolism and a preventive effect of high-dose riboflavin were reported. To explore the relation between the two, we tested if the therapeutic response to riboflavin is associated with specific mitochondrial DNA (mtDNA) haplogroups. We focused our attention on haplogroup H, which is known to differ from others in terms of energy metabolism. METHODS: Sixty-four migraineurs completed a 4-month open trial with riboflavin (400 mg QD) and were genotyped blindly for mtDNA haplogroups. RESULTS: Forty patients responded to riboflavin treatment and 24 were nonresponders. The mtDNA haplogroup H was found in 29 subjects (20 migraine without aura, 9 migraine with aura). Riboflavin responders were more numerous in the non-H group (67.5%). Conversely, nonresponders were mostly H (66.7%). The difference between the two groups was significant (chi(2) = 7.07; p = 0.01). The presence of aura had no influence on riboflavin's effectiveness (chi(2) = 0.113; p = 0.74) and was not associated with a particular haplogroup (chi(2) = 0.55; p = 0.46). CONCLUSIONS: In this pharmacogenetic study, riboflavin appears to be more effective in patients with migraine with non-H mitochondrial DNA haplotypes. The underlying mechanisms are unknown, but could be related to the association of haplogroup H with increased activity in complex I, which is a major target for riboflavin. Our results may have ethnic implications, since haplogroup H is chiefly found in the European population. [less ▲]

Mitochondrial function plasticity in Acanthamoeba castellanii during growth in batch culture.

in Journal of Bioenergetics & Biomembranes (2007), 39

The alterations in mitochondrial bioenergetics during growth in a batch culture of Acanthamoeba castellanii were studied. The capacity of cytochrome pathway-dependent respiration measured in vitro ... [more ▼]

The alterations in mitochondrial bioenergetics during growth in a batch culture of Acanthamoeba castellanii were studied. The capacity of cytochrome pathway-dependent respiration measured in vitro decreased from the intermediary phase, when cell division slowed down. The pattern of the cytochrome pathway capacity changes was paralleled from the intermediary phase by alterations in the amount of total (and reducible) membranous ubiquinone. These changes were accompanied by a decrease in mitochondrial reactive oxygen species production in vitro (when no energy-dissipating system was active), and almost no change in superoxide dismutase activity and protein level, thus indicating an equivalent need for this enzyme in oxidative stress defence in A. castellanii culture. On the other hand, a decrease in the activity and protein level of alternative oxidase and uncoupling protein was observed in vitro, when cells shifted from the exponential growth phase to the stationary phase. It turned out that the contribution of both energy-dissipating systems in the prevention of mitochondrial reactive oxygen species generation in vivo could lead to its constant level throughout the growth cycle of A. castellanii batch culture. Hence, the observed functional plasticity insures survival of high quality cysts of A. castellanii cells. [less ▲]

Mitochondrial genetics and alternative oxidases in Chlamydomonas reinhardtii

Conference (2005)

The mitochondrial genome

in Stern, David; Harris, Elizabeth; Witman, George (Eds.) The Chlamydomonas Sourcebook 3-vol set, 1-3 (2009)

Mitochondrial metabolite carrier family, topology, structure and functional properties: an overview.

in Acta Biochimica Polonica. Polish. (1996), 43(2), 349-360

A set of metabolite carriers operates the traffic of numerous molecules consumed or produced in mitochondrial matrix and/or cytosolic compartments. As their existence has been predicted by the ... [more ▼]

A set of metabolite carriers operates the traffic of numerous molecules consumed or produced in mitochondrial matrix and/or cytosolic compartments. As their existence has been predicted by the chemiosmotic theory, the first challenge, in the late sixties, was to prove their presence in the inner mitochondrial membrane and to describe the various transports carried out. The second challenge was to understand their mechanisms by the kinetic approach in intact mitochondria (seventies). The third challenge (late seventies-eighties) was to isolate and to reconstitute the carriers in liposomes in order to characterize the proteins and to establish the concept of a structural and a functional family as well as some structure-function relationship with the help of primary sequences. Genetics, molecular biology and genomic sequencing bring the fourth challenge (nineties): a raising number of putative carriers becomes known only by their primary sequences but their functions have to be discovered. The actual challenge of the future is the elucidation of the ternary structure of carrier proteins that together with site-directed mutagenesis and kinetic mechanism will permit to advance in the understanding of molecular mechanisms of transport processes. [less ▲]

Mitochondrial NADH:ubiquinone oxidoreductase (complex I) in eukaryotes: A highly conserved subunit composition highlighted by mining of protein databases

in Biochimica et Biophysica Acta-Bioenergetics (2011), 11

Complex I (NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain. Compared to its bacterial counterpart which encompasses 14-17 subunits, mitochondrial complex I has ... [more ▼]

Complex I (NADH:ubiquinone oxidoreductase) is the largest enzyme of the mitochondrial respiratory chain. Compared to its bacterial counterpart which encompasses 14-17 subunits, mitochondrial complex I has almost tripled its subunit composition during evolution of eukaryotes, by recruitment of so-called accessory subunits, part of them being specific to distinct evolutionary lineages. The increasing availability of numerous broadly sampled eukaryotic genomes now enables the reconstruction of the evolutionary history of this large protein complex. Here, a combination of profile-based sequence comparisons and basic structural properties analyses at the protein level enabled to pinpoint homology relationships between complex I subunits from fungi, mammals or green plants, previously identified as "lineage-specific" subunits. In addition, homologs of at least 40 mammalian complex I subunits are present in representatives of all major eukaryote assemblages, half of them having not been investigated so far (Excavates, Chromalveolates, Amoebozoa). This analysis revealed that complex I was subject to a phenomenal increase in size that predated the diversification of extant eukaryotes, followed by very few lineage-specific additions/losses of subunits. The implications of this subunit conservation for studies of complex I are discussed. [less ▲]

Mitochondrial oxidative phosphorylation injuries occurring in situ and in vitro.

in Transplantation Proceedings (1995), 27

Mitochondrial phylogeography of the edible dormouse (Glis glis) in the western Palearctic region

in Journal of Mammalogy (2010), 91(1), 233-242

This study describes in detail the phylogeoraphic pattern Of the edible dormouse (Glis glis) a European rodent With pronounced hibernating behavior We Used sequences of 831 base pairs of the mitochondrial ... [more ▼]

This study describes in detail the phylogeoraphic pattern Of the edible dormouse (Glis glis) a European rodent With pronounced hibernating behavior We Used sequences of 831 base pairs of the mitochondrial DNA cytochrome-b gene from 130 edible dormice collected at 43 localities (throughout Its distribution. Our results reveal presence of 3 main haplogroups: Sicilian, South Italian (restricted to the Calabrian region) (a widespread lineage corresponding to all remaining western, central. and eastern European populations). Examination of paleontological data confirms refugial regions for G,Its in the 3 Mediterranean peninsulas, although overall low genetic diversity is found. The low diversity of the European lineage Is probably the result refugium. Other factors, such as the of a recent expansion (dated around 2.000( years ago) from a single ecological constraints oil the species, way have caused genetic bottlenecks that reinforced the low genetic variability of G glis. This work could have important implications for strategies to conserve the edible dormouse by defining important areas for their conservation DOI: 10.1644/08-MAMM-A-392R1.1 [less ▲]

Mitochondrial Physiology Network: Mitochondrial respiration in permeabilized muscle fibers: needle biopsy from horse skeletal muscle

in Gnaiger, Erich (Ed.) MipNet Publications (2007)

1 Introduction ..........................................................1 2 The Protocol: Respiratory States .............................2 2.1 The O2k demo experiment ... [more ▼]

1 Introduction ..........................................................1 2 The Protocol: Respiratory States .............................2 2.1 The O2k demo experiment ...................................2 2.2 Preparation of permeabilized fibres .......................3 2.3 The experimental protocol ....................................3 3 References ............................................................4 [less ▲]