A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain.

Thirty-five years ago, we described fragmentation of the mitochondrial population in a living cell into small vesicles (mitochondrial fission). Subsequently, this phenomenon has become an object of general interest due to its involvement in the process of oxidative stress-related cell death and having high relevance to the incidence of a pathological phenotype. Tentatively, the key component of mitochondrial fission process is segregation and further asymmetric separation of a mitochondrial body yielding healthy (normally functioning) and impaired (incapable to function in a normal way) organelles with subsequent decomposition and removal of impaired elements through autophagy (mitophagy). We speculate that mitochondria contain cytoskeletal elements, which maintain the mitochondrial shape, and also are involved in the process of intramitochondrial segregation of waste products. We suggest that perturbation of the mitochondrial fission/fusion machinery and slowdown of the removal process of nonfunctional mitochondrial structures led to the increase of the proportion of impaired mitochondrial elements. When the concentration of malfunctioning mitochondria reaches a certain threshold, this can lead to various pathologies, including aging. Overall, we suggest a process of mitochondrial fission to be an essential component of a complex system controlling a healthy cell phenotype. The role of reactive oxygen species in mitochondrial fission is discussed.

A kidney is an organ with relatively low basal cellular regenerative potential. However, renal cells have a pronounced ability to proliferate after injury, which undermines that the kidney cells are able to regenerate under induced conditions. The majority of studies explain yielded regeneration either by the dedifferentiation of the mature tubular epithelium or by the presence of a resident pool of progenitor cells in the kidney tissue. Whether cells responsible for the regeneration of the kidney initially have progenitor properties or if they obtain a “progenitor phenotype” during dedifferentiation after an injury, still stays the open question. The major stumbling block in resolving the issue is the lack of specific methods for distinguishing between dedifferentiated cells and resident progenitor cells. Transgenic animals, single-cell transcriptomics, and other recent approaches could be powerful tools to solve this problem. This review examines the main mechanisms of kidney regeneration: dedifferentiation of epithelial cells and activation of progenitor cells with special attention to potential niches of kidney progenitor cells. We attempted to give a detailed description of the most controversial topics in this field and ways to resolve these issues.

The mitochondrial membrane potential (∆Ψ) is the driving force providing the electrical component of the total transmembrane potential of hydrogen ions generated by proton pumps, which is utilized by the ATP synthase. The role of ∆Ψ is not limited to its role in bioenergetics since it takes part in other important intracellular processes, which leads to the mandatory requirement of the homeostasis of ∆Ψ. Conventionally, ∆Ψ in living cells is estimated by the fluorescence of probes such as rhodamine 123, tetramethylrodamine, etc. However, when assessing the fluorescence, the possibility of the intracellular/intramitochondrial modification of the rhodamine molecule is not taken into account. Such changes were revealed in this work, in which a comparison of normal (astrocytic) and tumor (glioma) cells was conducted. Fluorescent microscopy, flow cytometry, and mass spectrometry revealed significant modifications of rhodamine molecules developing over time, which were prevented by amiodarone apparently due to blocking the release of xenobiotics from the cell and their transformation with the participation of cytochrome P450. Obviously, an important role in these processes is played by the increased retention of rhodamines in tumor cells. Our data require careful evaluation of mitochondrial ∆Ψ potential based on the assessment of the fluorescence of the mitochondrial probe.

There has been an explosion of interest in the use of uncouplers of oxidative phosphorylation in mitochondria in the treatment of several pathologies, including neurological ones. In this review, we analyzed all the mechanisms associated with mitochondrial uncoupling and the metabolic and signaling cascades triggered by uncouplers. We provide a full set of positive and negative effects that should be taken into account when using uncouplers in experiments and clinical practice.

The use of stem cells is part of a strategy for the treatment of a large number of diseases. However, the source of the original stem cells for use is extremely important and determines their therapeutic potential. Mesenchymal stromal cells (MSC) have proven their therapeutic effectiveness when used in a number of pathological models. However, it remains an open question whether the chronological age of the donor organism affects the effectiveness of the use of MSC. The asymmetric division of stem cells, the result of which is some residential stem cells acquiring a non-senile phenotype, means that stem cells possess an intrinsic ability to preserve juvenile characteristics, implying an absence or at least remarkable retardation of senescence in stem cells. To test whether residential MSC senesce, we evaluated the physiological changes in the MSC from old rats, with a further comparison of the neuroprotective properties of MSC from young and old animals in a model of traumatic brain injury. We found that, while the effect of administration of MSC on lesion volume was minimal, functional recovery was remarkable, with the highest effect assigned to fetal cells; the lowest effect was recorded for cells isolated from adult rats and postnatal cells, having intermediate potency. MSC from the young rats were characterized by a faster growth than adult MSC, correlating with levels of proliferating cell nuclear antigen (PCNA). However, there were no differences in respiratory activity of MSC from young and old rats, but young cells showed much higher glucose utilization than old ones. Autophagy flux was almost the same in both types of cells, but there were remarkable ultrastructural differences in old and young cells.