The significant destructive changes in ultrastructure of hepatocytes from laboratory mice kept in different vivariums in Moscow and fed with dry laboratory animal diets acquired from different ...domestic manufacturers that were not standardized for initial products were demonstrated using electron microscopy. Furthermore, disruption in the ultrastructure of liver parenchymal cells occurred regardless of the animal status (SPF or conventional), conditions of various vivariums, as well as the feed manufacturer. At the same time, studies on ultrastructure of liver hepatocytes from mice kept in the Charles River Laboratory facilities in Germany and fed with the Altromin Spezialfutter laboratory animal diet (GmbH & Co., Germany) that was produced using quality control of ingredients did not reveal destructive changes in the internal ultrastructure of hepatocytes. However, if these mice were later fed with the food produced in local manufactures, changes in the structure of liver cells developed after 2 months. Thus, feeding with dry diet from the domestic producers of an unspecified composition causes significant changes in the ultrastructure of hepatocytes in control animals, reflecting the development of some pathological processes in the body.
Mitochondrial ultrastructure in cardiomyocytes from 3- and 24-month-old Wistar and OXYS rats was investigated using a new approach designed for morphometric analysis. The data fully confirm the ...electron microscopy data: the area of the inner mitochondrial membrane per unit volume of mitochondria was significantly decreased with age, as found on heart muscle section. In 3-month-old Wistar rats from the control group, this parameter was 41.3 ± 1.52 μm
2
/μm
3
, where-as in OXYS rats it was decreased to 30.57 ± 1.74 μm
2
/μm
3
. With age, an area of the inner mitochondrial membrane per unit volume of mitochondria declined in both rat strains: Wistar — from 41.3 ± 1.52 to 21.47 ± 1.22 μm
2
/μm
3
, OXYS — from 30.57 ± 1.74 to 16.3 ± 0.89 μm
2
/μm
3
. A new method that we designed and used for morphometric analysis notably simplifies the process of morphometric measurements and opens up good opportunities for its further optimization using image recognition technology.
Mitochondrial reactive oxygen species regulate many important biological processes. We studied H₂O₂ formation by nonsynaptic brain mitochondria in response to the addition of low concentrations of ...glutamate, an excitatory neurotransmitter. We demonstrated that glutamate at concentrations from 10 to 50μM stimulated the H₂O₂ generation in mitochondria up to 4-fold, in a dose-dependent manner. The effect of glutamate was observed only in the presence of Ca²⁺ (20μM) in the incubation medium, and the rate of calcium uptake by the brain mitochondria was increased by up to 50% by glutamate. Glutamate-dependent effects were sensitive to the NMDA receptor inhibitors MK-801 (10μM) and D-AP5 (20μM) and the inhibitory neurotransmitter glycine (5mM). We have shown that the H₂O₂ formation caused by glutamate is associated with complex II and is dependent on the mitochondrial potential. We have found that nonsynaptic brain mitochondria are a target of direct glutamate signaling, which can specifically activate H₂O₂ formation through mitochondrial respiratory chain complex II. The H₂O₂ formation induced by glutamate can be blocked by glycine, an inhibitory neurotransmitter that prevents the deleterious effects of glutamate in brain mitochondria.
The ultrastructure of mitochondria in the flattened circomyarian fibers of the horsehair worm
Gordionus alpestris
(Nemathelminthes) was examined. In contrast to the previously published data, we ...showed these mitochondria to be giant elongated organelles that densely fill the central cytoplasmic space of the ribbon-like muscle fibers. No fundamental differ-ences were found in the ultrastructure of the muscle tissue mitochondria in actively moving free-living and parasitic
G. alpestris
worms. The functional significance of the observed ultrastructural organization of mitochondria is discussed in connection with the necessity for an extended mitochondrial membrane system for a uniform supply of active muscle tissue with energy.
Morphometric analysis of mitochondria in skeletal muscles and heart of 6- and 60-month-old naked mole rats (
Heterocephalus glaber
) revealed a significant age-dependent increase in the total area of ...mitochondrial cross-sections in studied muscle fibers. For 6- and 60-month-old animals, these values were 4.8 ± 0.4 and 12.7 ± 1.8%, respectively. This effect is mainly based on an increase in the number of mitochondria. In 6-month-old naked mole rats, there were 0.23 ± 0.02 mitochondrial cross-sections per μm
2
of muscle fiber, while in 60-month-old animals this value was 0.47 ± 0.03. The average area of a single mitochondrial cross-section also increased with age in skeletal muscles–from 0.21 ± 0.01 to 0.29 ± 0.03 μm
2
. Thus, naked mole rats show a drastic enlargement of the mitochondrial apparatus in skeletal muscles with age due to an increase in the number of mitochondria and their size. They possess a neotenic type of chondriome accompanied by specific features of mitochondrial functioning in the state of oxidative phosphorylation and a significant decrease in the level of matrix adenine nucleotides.
—
Internal ultrastructure of the muscle tissue mitochondria of horsehair worm
Gordionus alpestris
(Nematomorpha) was studied using morphometry. Surface area of the inner mitochondrial membrane per ...unit of the mitochondrial volume, or surface density of the inner mitochondrial membrane, was measured as a main morphometric parameter. The surface density of the inner mitochondrial membrane of the
G. alpestris
muscle tissue was compared to the respective parameter of the skeletal and cardiac muscle mitochondria. The surface density of the inner mitochondrial membrane of the worm was close to the surface density values of the cardimyocytes of 3-month-old mice and Wistar rats and was slightly higher than the surface density of mitochondria from the skeletal muscle of 3-month-old mice. The functional significance of the well-developed system of mitochondrial membranes of extended mitochondria of the horsehair worm is discussed as a structure necessary to ensure effective functioning of the circomyarian conntractile apparatus in the muscle tissue of the horsehair worm.
We studied age-related ultrastructural reorganization in acinar cells and intercalary ducts of the lacrimal gland acini in 3-, 15-, and 24-month-old Wistar rats. Ultrastructural changes in the ...lacrimal gland progressed with age and led to dramatic ultrastructural reconstruction of the lacrimal gland at the age of 24 months. These changes mainly included complete destruction of acinar cells and increase in the number of enlarged branched ducts that fi lled the greater part of gland volume; these dusts were lined with epithelial cells with altered ultrastructure. Acinar cells in the acini communicate via special connecting intermembrane complexes formed by desmosomes and mitochondria adjacent to them in each contacting cell. It is assumed that association of mitochondria with desmosomes found in the acini is a special functional complex indicating that every single acinus is a functional formation. This assumption is indirectly confi rmed by the fact that the destruction never occurred in a single cell, but always involved all cells constituting the acini. The revealed ultrastructural changes refl ect age-related deterioration of the secretory function of the lacrimal gland.
According to previous studies, ADP/ATP carrier (AAC) can possibly exist as a monomer or in a dimer state in the inner mitochondrial membrane; however, the question on its functional oligomeric state ...is still open. The aim of the present work is to establish the external factors that could control the functional oligomeric state of AAC (i.e., monomer or dimer). The study is based on the results of our previous work, which revealed that the volume regulation system of mitochondria (MVRS) affects the oxidative phosphorylation (OXPHOS) system: MVRS could transfer OXPHOS system functioning in a state of supercomplex. Consequently, one may expect that the volume regulation system could also control the functional state of AAC during phosphorylation. Here, on rat liver mitochondria we show that, depending on the incubation medium tonicity, AAC functions in two different ways: either as a monomer (in hypotonic and isotonic media) or as a dimer (in a hypertonic medium). Thus, the transition between the monomeric and dimeric forms of AAC is regulated by MVRS, as well as by functioning of OXPHOS. We conclude that the structural reorganization of AAC is associated with the entire OXPHOS reorganization into a supercomplex. It was also found that dimerization of AAC can occur not only due to the action of MVRS (in hypotonic media) but also under hypoxic conditions.
A comparative electron microscopic and morphometric analysis of age-related transformations in the ultrastructure of the skeletal muscle mitochondrial apparatus was carried out in animal species with ...different aging programs: short-lived classical objects, such as C57BL/6 mice and Wistar rats, prematurely aging OXYS rats, and the longest-living rodents, naked mole-rats (
Heterocephalus glaber
), characterized by delayed aging. In C57BL/6 mice, age-related reorganization of the skeletal muscle mitochondrial apparatus corresponds to that reported previously for Wistar rats: the mitochondrial reticulum forms by the age of 2.5–3 months; by the age of 30 months, it undergoes a drastic reduction, due to which the number of mitochondrial cross-sections in muscle fibers decreases almost twofold, from 0.45 ± 0.074 to 0.23 ± 0.017 profiles per µm
2
. In C57BL/6 mice, no destructive changes in the mitochondrial ultrastructure were observed, in contrast to OXYS rats, in which age-related changes in the chondriome affect both the overall structure and internal ultrastructure of the muscle fiber mitochondrial apparatus. At the same time, in naked mole-rats, which are comparable with mice in their size, the number and size of mitochondria in skeletal muscles increase significantly by the age of five years, although no mitochondrial reticulum forms. It is hypothesized that a special organization of the mitochondrial apparatus in naked mole-rat skeletal muscles provide a proper level of redox processes in muscles, thus preventing a decline in their physical efficiency and the development of sarcopenia, whereas in C57BL/6 mice, Wistar and OXYS rats, age-related abnormalities in the structural organization of skeletal muscle mitochondrial apparatus may be one of the major causes for the development of age-related pathologies, including sarcopenia.
A comparative electron microscopic and morphometric analysis of age-related transformations in the ultrastructure of the skeletal muscle mitochondrial apparatus was carried out in animal species with ...different aging programs: short-lived classical objects, such as C57BL/6 mice and Wistar rats, prematurely aging OXYS rats, and the longest-living rodents, naked mole-rats (Heterocephalus glaber), characterized by delayed aging. In C57BL/6 mice, age-related reorganization of the skeletal muscle mitochondrial apparatus corresponds to that reported previously for Wistar rats: the mitochondrial reticulum forms by the age of 2.5–3 months; by the age of 30 months, it undergoes a drastic reduction, due to which the number of mitochondrial cross-sections in muscle fibers decreases almost twofold, from 0.45 ± 0.074 to 0.23 ± 0.017 profiles per µm2. In C57BL/6 mice, no destructive changes in the mitochondrial ultrastructure were observed, in contrast to OXYS rats, in which age-related changes in the chondriome affect both the overall structure and internal ultrastructure of the muscle fiber mitochondrial apparatus. At the same time, in naked mole-rats, which are comparable with mice in their size, the number and size of mitochondria in skeletal muscles increase significantly by the age of five years, although no mitochondrial reticulum forms. It is hypothesized that a special organization of the mitochondrial apparatus in naked mole-rat skeletal muscles provide a proper level of redox processes in muscles, thus preventing a decline in their physical efficiency and the development of sarcopenia, whereas in C57BL/6 mice, Wistar and OXYS rats, age-related abnormalities in the structural organization of skeletal muscle mitochondrial apparatus may be one of the major causes for the development of age-related pathologies, including sarcopenia.
